1. Epidemiology of Diabetes mellitus in Puerto Rico
Efraín Rodríguez Vigil, MD FACP, FACE
Medical Director
Center for Diabetes Control Inc.

2. Objetives
Discuss new diagnostic test and classification for diabetes mellitus
Discuss the epidemiologic data for diabetes mellitus in PR
Discuss the role of diabetes mellitus in cognitive disorders

3. Disclosures
Nothing to disclose

4. Types of Diabetes Type 1: Autoimmune Type 2: Insulin Resistance
Type 1: Autoimmune
Type 2: Insulin Resistance
Gestational: Insulin resistance
Secondary Diabetes: Tumors, medication, etc.

5. Five Clusters of Diabetes
N (%)
Characteristics
Name 1
577 (6.4)
Early disease onset (at a young age), essentially corresponds with type 1 diabetes and LADA, relatively low BMI, poor metabolic control, insulin deficiency (impaired insulin production), GADA+
Severe autoimmune diabetes (SAID) 2
1575 (17.5)
Similar to cluster 1 but GADA–, high HbA1c, highest incidence of retinopathy
Severe insulin-deficient diabetes (SIDD) 3
1373 (15.3)
Insulin resistance, high BMI, highest incidence of nephropathy
Severe-insulin resistant diabetes (SIRD) 4
1942 (21.6)
Obesity, younger age, not insulin resistant
Mild obesity-related diabetes (MOD) 5
3513 (39.1)
Older age, modest metabolic alterations
Mild age-related diabetes (MARD)

6. Criteria for the Diagnosis of Diabetes
Fasting plasma glucose (FPG) ≥126 mg/dL (7.0 mmol/L) OR
2-h plasma glucose ≥200 mg/dL (11.1 mmol/L) during an OGTT
A1C ≥6.5%
Classic diabetes symptoms + random plasma glucose ≥200 mg/dL (11.1 mmol/L)
Fasting plasma glucose, the 2 hour plasma glucose after a 75-g oral glucose tolerance test, and A1C are equally appropriate diagnostic tests for diabetes.
These diagnostic criteria are:
Fasting plasma glucose (FPG) ≥126 mg/dL OR
2-hour plasma glucose ≥200 mg/dL during an OGTT
A1C ≥6.5%
Or in a patient with classic symptoms of hyperglycemia a random plasma glucose ≥ 200 can also be used.
In the absence of unequivocal hyperglycemia, the result should be confirmed by repeat testing.
[SLIDE]
American Diabetes Association Standards of Medical Care in Diabetes. Classification and diagnosis of diabetes. Diabetes Care 2017; 40 (Suppl. 1): S11-S24
Reference
American Diabetes Association. Standards of medical care in diabetes—2014. Diabetes Care 2014;37(suppl 1):S15; Table 2 6

7. Criteria for the Diagnosis of Diabetes Mellitus
Fasting Glucose
2-h Glucose Tolerance Test
HbA1c
Diabetes
Diabetes
Diabetes
126 mg/dL
Impaired Fasting
Glucose
200 mg/dL
Impaired Glucose
Tolerance
Increased risk for diabetes
6.5%
100 mg/dL
Healthy
140 mg/dL
Healthy
Healthy
5.7%
Diabetes Care 2010;34:Supp1:S1. 7

8. Glucose Tolerance Test
Oral Tolerance Test: 8 hours fasting
75 gms of Glucola™
Blood sample at:
0 min
30 min
60 min
120 min
180 min

9. Epidemiology Definition
Epidemiology is the branch of medical science that deals with the incidence, distribution, and control of disease in a population. Is considered  the sum of the factors controlling the presence or absence of a disease or pathogen.

10. Important Definitions
Incidence: Number of new cases/ period of time
Mortality: Number of deaths/ period of time
Prevalence: Number of cases at a given point in time
Population at risk: comprises the total number of individuals in original population that are considered capable of acquiring the particular disease or disease characteristic being studied.
Trend: A pattern of gradual change in a condition, output, or process, or an average or general tendency of a series of data points to move in a certain direction over time, represented by a line or curve on a graph.

11. Types of Risk Factors Factors Causally Associated with
Factors that are Prime Targets for Major Population Policies
Factors Causally Associated with
Increased Diabetes Incidence in Individuals
Modifiable and Prime
Targets for Individual-Level Interventions
Factors Explaining
Population Trends in the Disease
Structured, multi-disciplinary lifestyle
Metformin and other drugs
Nutrition / education referral
Brief Counseling
Food policy incentives and restrictions; Crop subsidy policies
Incentives / restrictions related to built environment
Youth-targeted obesity prevention

12. Risk Factors for Diabetes mellitus Development
Non Modifiable
Genetics
Age
Sex
Ethnicity
Poor fetal growth
High birth weight
Modifiable
Weight
Obesity *
Physical inactivity*
Smoke
Unhealthy diet*
* Strongest risk factor

13. Normal BMI by Height If you are not Asian American or Pacific Islander
If you are Asian American
If you are Pacific Islander
 At-risk BMI ≥ 25
 At-risk BMI ≥ 23
 At-risk BMI ≥ 26
Height
Weight
 4'10"
119
110
124
 4'11"
114
128
 5'0"
118
133
 5'1"
132
122
137
 5'2"
136
126
142
 5'3"
141
130
146
 5'4"
145
134
151
 5'5"
 150
138
156
 5'6"
155
161
 5'7"
159
166
 5'8"
164
171
 5'9"
 169
176
 5'10"
 174
160
181
 5'11"
 179
165
186
 6'0"
 184
169
191
 6'1"
 189
174
197
 6'2"
 194
179
202
 6'3"
 200
184
208
 6'4"
 205
189
6'4"
213

14. Body Mass Index and 1-year Risk of Diabetes
(Ford ES et al. AJE 1997;146:214-22)
%- Point
Absolute Increase
0.031
0.204
0.315
0.329
0.675
0.850
1.256
1.668
2.237
Increase per
100,000 31
204
315
329
675
850
1,256
1,668
2,237
Cumulative
Increase
BMI
<22
22-<23
23-<24
24-<25
25-<27
27-<29
29-<31
31-<33
33-<35
35+
1-y Risk (%)
0. 224
0. 255
0. 428
0. 539
0. 553
0. 899
1.074
1.480
1.892
2.461 RR 1
1.18
2.44
2.97
3.04
5.07
5.70
8.21
10.89
14.64
550
1,554
7,565

15. Diabetes mellitus Prevalence in PR 2000 - 2015

16. Prevalence of Diabetes mellitus by Year and Sex

17. Prevalence of Diabetes mellitus in Puerto Rico by Sex

18. Prevalence of Diabetes mellitus in PR by Age Group

19. Prevalence of Diabetes mellitus in PR Adjusted by Income

20. Prevalence of Diabetes mellitus in PR by Education Attained

21. Prevalence of Obesity in PR

22. Obesity in PR by Household Income

23. How are we doing?

24. Distribution by Sex and Age Groups
Female
Male
Total
18 – 29 4
30 – 39 15 19
40 – 49 28 38 66
50 – 59 73 55
128
60 – 69
129 71
200
70 – 79 95 63
158
> 80 10 25
344
256
600
* 85% are > 50 years, 90% female are > 50 years and 78% male are > 50 years

25. Diabetes and Obesity 2011

27. Diabetes and Obesity Prevalence in PR

28. Prevalence of Hypertension and Hypercholesterolemia (2011) in a Diabetic Population

29. Diabetes mellitus Control

30. Blood Pressure

31. Lipids Control (Calculated LDL)

32. Eye Examination, Monitoring, Education and A1c Monitoring

33. Diabetes Foot Examination

34. Influenza and Pneumococcus Vaccination

35. Diabetes Preventive Measures

36. A1c Measure, Self Monitoring Blood Glucose and Education

37. Risk Factor Control in Adults With Diabetes (PRADCO)

38. Diabetes mellitus Chronic Complications (2012)
Retinopathy 20%
Cardiovascular Disease 14%
Peripheral Neuropathy 67%
Depression %

39. Cognitive Dysfunction in Diabetes mellitus
CDC, Inc.

40. Cognitive Impairment in Diabetes mellitus
Affected Areas:
Attention
Learning and memory
Mental flexibility
Psychomotor efficiency
Speed and executive functions
CDC, Inc.

41. Diabetes and Dementia
Type 1 Diabetes: mild to moderate slowing of mental speed and diminished mental flexibility
Type 2 Diabetes: cognitive changes affect learning, memory, mental flexibility and mental speed
The rate of cognitive decline is accelerated in elderly people with type 2 diabetes
T2 DM or impaired fasting glucose may be present in 80% of people with Alzheimer’s disease
(Janson et al, Diabetes 2004;83)

42. Emerging complications of diabetes
Improvement in management of microvascular complications (due to improved glycemic, blood pressure control ) and macrovascular complications (improved lipid control)
People with diabetes are living longer
Emergence of novel complications such as cognitive impairment and dementia
Mediated by mechanisms not addressed by conventional therapies

43. Center for Disease Control database for deaths in 2010.
Aging Drives Disease
Center for Disease Control database for deaths in 2010.

44. Alzheimer’s Disease Prevalence is increasing especially in those age 85+

45. Diabetes mellitus and Depression Prevalence

46. Metanalysis of 16 studies assessing the risk of dementia with diabetes
Incidence of any dementia was increased in people with diabetes in 5 of 7 studies
Overall, the incidence of dementia was increased by % relative to people without diabetes (CV factors not controlled in all)
Increased risk of Alzheimer's disease % (7 of 11 studies)
Increase in risk of vascular dementia of % (6 of 7 studies)
Biessels et al. Lancet Neurology 5(1); Jan 2006

47. Accelerated Progression from Mild Cognitive Impairment to Dementia in People with Diabetes
Weili Xu et al. Diabetes. 2010;59(11):

48. Predictors of cognitive impairment and dementia in older people with diabetes
Surviving participants of the Fremantle Diabetes Study (FDS), who were aged 70 years
Of 302 participants, 28 (9.3%) had dementia (16 with probable Alzheimer’s disease) and 60 (19.9%) had cognitive impairment without dementia
The major independent longitudinal predictors of dementia were
older age (per decade; odds ratio 4.0)
diabetes duration (for each 5 years; odds ratio 1.69)
peripheral arterial disease (odds ratio 5.35)
exercise (which was protective; odds ratio 0.26)
For Alzheimer’s disease, diabetes duration was an independent predictor in addition to age and diastolic blood pressure
Bruce et al. Diabetologia Feb 2008

49. Determinants of the risk of dementia in individuals with diabetes.
Biessels et al. Lancet Neurology 5(1); Jan 2006

50. Mechanisms that may link diabetes and dementia
Exalto et al. Exp Gerontol. 47 (11) Nov 2012

51. Potential mediators of cognitive impairment in patients with type 2 diabetes mellitus.
Nature Endo Rev 7; Feb 2011

52. The role of inflammation
Inflammation is now thought to be involved in insulin resistance and the development of diabetes
Human studies point towards increased inflammatory biomarkers (IL-6 and TNF) and age-related cognitive impairment
One cross-sectional study in T2DM suggests association between cognitive ability and Il-6

53. T2DM is associated with the development of vascular dysfunction in the brain.
T2DM is a risk factor for microvascular complications as well as macrovascular defects such as stroke
Chap 16; Mental and Behavioral disorders; Diseases of the Nervous System Feb 2013

54. Hypothalamic-pituitary-adrenal dysregulation in diabetes
People with T2DM have activation of the hypothalamic-pituitary-adrenal (HPA) axis
Raised levels of cortisol and adrenocorticotrophic hormone (ACTH)
Increased cortisol levels are associated with increased heart disease and diabetic complications
Dysregulation of the HPA axis may be associated with accelerated cognitive decline and mood disturbances in patients with T2DM

55. Glucocorticoids and cognitive decline
Chronic exposure of the hippocampus to high levels of glucocorticoids (cortisol) thought to contribute to age-related cognitive decline
Patients with Alzheimer’s have high cortisol levels and low hippocampal volumes
Studies in T2DM suggest high cortisol levels are associated with accelerated cognitive decline, reduced working memory, processing speed, mental flexibility, immediate and delayed memory (Edinburgh Type 2 Diabetes Study)

56. Glucocorticoids and depression
Depression is a well-established risk factor for cognitive impairment
Depression and its symptoms are more common in people with diabetes mellitus
One study in participants both with and without T2DM, reported high cortisol levels and more depressive symptoms were associated with high blood glucose levels
This effect was stronger in African American participants (who have a high incidence of both diabetes and depression) than in white individuals
Boyle, S. H. et al. Diabetes Care 30, (2007)

57. What can be done to reduce the development of dementia in diabetes
Blood pressure control?
Better control of diabetes?
Avoidance of hypoglycemia
Statins?
Treat depression?

58. Does treatment of diabetes make a difference?
Prospective study of type 2 diabetes and cognitive decline in women aged years. Nurses' health study in the US; two cognitive interviews were carried out by telephone during
Women with type 2 diabetes performed worse on all cognitive tests than women without diabetes at baseline (odds ratios 1.34)
In contrast, women with diabetes who were on oral hypoglycemic agents performed similarly to women without diabetes (OR 1.06 and 0.99)
Women not using any medication had the greatest odds of poor performance (OR 1.74 and 1.45)
Women with type 2 diabetes have about 30% greater odds of poor cognitive function than those without diabetes, with a 50% increase after 15 years' of diabetes
(Logroscino et al. BMJ 2004, Mar 6)

59. Effects of intensive glucose lowering on brain structure and function in people with type 2 diabetes (ACCORD MIND)
Participants (aged 55–80 years) with T2DM, high HbA 1c concentrations (>7·5%; >58 mmol/mol), and a high risk of cardiovascular events:
The Digit Symbol Substitution Test (DSST) score, at baseline and at 20 and 40 months and total brain volume (TBV) by MRI, as a primary brain structure outcome
There was no significant treatment difference in mean 40-month DSST score (difference in mean 0·32, 95%;p=0·2997)
The intensive-treatment group had a greater mean TBV than the standard-treatment group (4·62, 2·0 to 7·3; p=0·0007)
Lancet Neurology, The, , Volume 10, Issue 11

60. Cognitive impairment affects management of diabetes and treatment-related complications
Less involvement on diabetes self-care and monitoring
Increased likelihood of severe hypoglycemia
Increased risk of major cardiovascular events and death
Increased risk of injurious falls

61. Copyright © 2012 American Medical Association. All rights reserved.
Hypoglycemic Episodes and Risk of Dementia in Older Patients With Type 2 Diabetes Mellitus
JAMA. 2009;301(15): doi: /jama
Date of download: 5/7/2013
Copyright © 2012 American Medical Association. All rights reserved.

62. Risk Factors For Severe Hypoglycemia
Age
Unawareness of, or previous severe hypoglycemia
High doses of insulin or sulfonylureas
Recent hospitalization or intercurrent illness
Polypharmacy (>5 prescribed meds)
“Tight control” of diabetes
Poor nutrition or fasting
Chronic liver, renal or cardiovascular disease
Vigorous sustained exercise
Endocrine deficiency (thyroid, adrenal, or pituitary)
Alcohol use
Loss of normal counter-regulation
Chelliah. Drugs aging 2004:21

63. Screening
Persons with diabetes are screened for retinopathy, neuropathy, microalbuminuria
Screening for peripheral arterial or cardiovascular disease if symptomatic
Cognitive impairment or dementia is often undiagnosed
Perceived lack of benefit of early diagnosis
How does this translate to persons with T2 DM?

64. Diagnosis
Work-up of any patient with T2DM and cognitive dysfunction is the same as any other patient with cognitive complaints
Behavior, mood and personality changes should be addressed
Assess diabetes management and support system
Serum chemistry, thyroid, B12, HIV, RPR as indicated
Neuroimaging (MRI if possible)

65. Cognitive trajectories in T2DM
Modest decline in cognition over time even in people without dementia
This affects verbal memory, information processing speed, attention and executive function
Modest decrements affect all age groups and are slowly progressive over time
These are NOT early manifestations of dementia
Dementia only affects a subset; possible added effect of Alzheimer’s or severe cerebrovascular disease?

66. What about MRI?
Multiple white matter areas of ischemia

67. Functional MRI showing less brain activation in diabetic subject
Gail Munsen PhD. Joslin Diabetes Center 2011
Diabetic subject
Control subject

68. Treatment
As yet there are no diabetes-specific therapies with proven efficacy in preventing or ameliorating cognitive decline
Cognitive function is being included as an outcome measure in more therapeutic trials
Glucose lowering does not show consistent benefit on cognition
The large ACCORD-MIND study showed that intensive glucose lowering treatment over 40 mth in people over 55 with T2DM did not benefit cognitive performance

69. Conclusion
Diabetes mellitus prevalence in PR has increased during the last decades
This correlated with an increase in obesity prevalence
Preventive measures has failed in improving stablished goals
Cognitive impairment or dementia is often undiagnosed
Education measure has to be changed if we want a real advance in the prevention of diabetes morbidity and mortality

70. Questions?
Thanks