Modifying Risk Factors to Prevent Type 2

DiabetesSumeet Goel, D.O.Family Medicine

Stevens Point, WIClass of 2010

Objectives

Review Diabetes

Review risk factors that lead to diabetes

Discuss how to Modify those risk factors

Discuss pharmacologic and lifestyle options that may maximize outcomes for patients at risk for developing diabetes

Pre-test Question #1Which of the following defines diabetes:

1)Fasting glucose of 126 or greater on 2 separate occasions

2)A1c 6.5 or above

3)Random (non-fasting) glucose above 200

4)Oral glucose tolerance test with 2 hour post-prandial above 200

5)All of the above

Pre-test Question #1 (Answer)Which of the following defines diabetes:

1)Fasting glucose of 126 or greater on 2 separate occasions

2)A1c 6.5 or above

3)Random (non-fasting) glucose above 200

4)Oral glucose tolerance test with 2 hour post-prandial above 200

5)All of the above

Pre-test Question #2Which of the following defines impaired fasting glucose (pre-diabetes)?

1)Fasting glucose of 100 or greater

2)A1c 6.0 or above

3)Oral glucose tolerance test with 2 hour post-prandial between 140 and 199

4)All of the above

Pre-test Question #2 (Answer)Which of the following defines impaired fasting glucose (pre-diabetes)?

1)Fasting glucose of 100 or greater

2)A1c 6.0 or above

3)Oral glucose tolerance test with 2 hour post-prandial between 140 and 199

4)All of the above

Introduction

Type 2 Diabetes is Characterized by:

Hyperglycemia

Insulin Resistance

Impairment of Insulin Secretion

Limited ability to predict and prevent Type 2 Diabetes in General Population

Who is most at risk?

Impaired Fasting Glucose/Impaired Glucose Tolerance

Obesity

Family History of Type 2 Diabetes

Certain Ethnic Groups (Asian, Hispanic, African American)

How do we prevent this?

First Step in Management is:

Lifestyle Changes

Tell me more

Lifestyle changes means?

Tell me more

and this?

Tell me more

Stop this?!?!

Stop this?!

I can still do this right?

Stop this?!

But this is legal...

well almost legal…

and not addictive.

Stop this?!

Wait now that’s crossing the line!

Easy fix.

I’ll just take these.

Early Pharmacologic Therapy

Pharmacologic Therapy (primarily metformin)

Clinical Trials have shown some ability to delay onset of diabetes but impact on CVD risk factors is less clear. (note: how does one define diabetes while on medication?)

Long-term benefits of early pharmacologic treatment versus withholding until diabetes develops are unproven.

Neither Lifestyle Changes nor pharmacologic therapy have been shown to reduce morbidity or mortality in patients at high risk for developing diabetes. That said, lifestyle changes are generally beneficial and do not have adverse effects.

Lifestyle Modification

Targeted population include those with A1c 5.7 - 6.4 (Impaired Fasting Glucose)

Emphasize benefit of weight loss & increased physical activity

Emphasize quitting smoking

Follow closely with at least annual laboratory evaluation with fasting glucose and lipid panel (foundation for biometric screening)

Lifestyle Modification

Lifestyle modifications delay onset of diabetes

Changes in diet/exercise show benefit even after progression to diabetes

Importance of these factors is further evidenced when looking at societies that have undergone westernization and the increase in diabetes prevalence that occurs

Can be marked by increased obesity in society

Diet (without weight loss)

Diet without weight loss does not show benefit for diabetes prevention.

Women’s Health Initiative Dietary Modification Trial (2008)

48,000 postmenopausal women (average age 62) randomly assigned to a regular diet or a low fat diet (20 percent reduction in caloric intake)

After follow-up 8 years later diabetes prevalence was the same in both groups and mean weight was about equal in both groups (difference of 2kg between groups)

This concept is difficult to study and this study had many flaws

Diet (without weight loss)

Mediterranean Diet:

Study in 2011 with 7447 participants (non-randomized)

High risk group cardiovascular group was assigned a low fat control diet

Remainder was assigned mediterranean diet with nuts or with virgin olive oil

Four year follow-up with lower incidence of diabetes in mediterranean diet groups (80 and 92 cases versus 101 cases in low fat control group)

Weight and physical activity was equal between groups.

Mediterranean Diet

Eating primarily plant-based foods (fruits, vegetables, whole grains, legumes, nuts)

Replacing Butter with olive oil or other healthy fats

Using Herbs/Spices instead of salt to flavor foods

Limiting Red Meat to less than a few times a month

Eating fish/poultry at least twice weekly

Red wine in moderation (optional)

Diet also recognizes importance of physical activity and enjoying meals with family/friends

Mediterranean Diet

Has role in heart health, chronic disease prevention, and long-term health benefits

Does not, however, have strong correlation with diabetes prevention

This statement is focused on a dietary change without associated weight loss.

Weight Loss

Weight reduction improves glycemic control and prevents onset of diabetes

Many different trials showing different interventions and their benefits:

Finnish Diabetes Prevention Study

Diabetes Prevention Program

China Da Qing Diabetes Prevention Study

Zensharen Study for Prevention of Lifestyle Disease

Finnish Diabetes Prevention Study

522 Middle-Aged patients (mean age 55 years) with impaired glucose tolerance were assigned to a weight-reduction and exercise program versus a control group

After 2 years the intervention group lost 3.5kg

Diabetes incidence in intervention group - 11% (23% in control group)

Additional 3 year follow-up without additional intervention showed reduced diabetes incidence (23% in intervention group versus 38% in control group)

China Da Qing Diabetes Prevention Study577 adults with impaired glucose tolerance were randomly assigned to a control group or one of three active intervention groups (diet, exercise, or both)

6 year followup

Intervention group diabetes incidence 72% vs 90%

CV Indicence 12% vs 20%

All cause mortality 28% vs 38%

Zensharen Study for Prevention of Lifestyle Diseases

641 Overweight Japanese patients with impaired fasting glucose assigned to diet/exercise program versus control group

After 3 years – incidence of type 2 diabetes showed greatest benefit in those at greatest risk of diabetes (A1c >5.6%)

No benefit of lifestyle intervention in group with isolated impaired fasting glucose

Diabetes Prevention Program

Much larger trial – 3,234 patients with impaired glucose tolerance and obesity:

Intensive Lifestyle group (aim reducing weight by 7% with behavioral modification, low fat diet, exercise 150 minutes per week).

Metformin 850mg bid plus information on diet and exercise

Placebo plus diet and exercise

Diabetes Prevention Program

Intensive lifestyle group: Fewest developed diabetes (14%)

Metformin + diet/exercise: 22%

Placebo plus diet/exercise: 29%

*Lifestyle intervention was effective in men and women in all age and ethnic groups

Diabetes Prevention Program

Average weight loss in intensive intervention group was 15 lbs (7%)

Diabetes prevention was most strongly correlated with weight loss as opposed to diet and exercise (16% risk reduction for every kilogram reduction in weight)

Smoking

Smoking increases systemic inflammation thereby reducing peripheral receptor sensitivity

Diabetes risk reduction with smoking cessation varies depending on individual risk factors

Smoking cessation can be associated with weight gain, however

In general smoking cessation is of paramount importance for diabetes prevention and obviously to minimize other associated comorbidities

Vitamin D

Several studies show an inverse relationship between circulating 25-hydroxyvitamin D levels and Type 2 diabetes risk

I.e. Low Vitamin D increases Type 2 Diabetes Risk

Intervention studies (testing/supplementation) show no effect on glycemic control

Intensive Lifestyle Modifications

Case #1

68 year old patient presents for routine physical exam. He is mildly overweight with BMI of 27.5 and has a fasting glucose of 104 with a creatinine of 0.8. Family history has 2nd degree relatives with type 2 diabetes. What would you recommend?

Intensive lifestyle intervention (at least 7% weight loss)

Lifestyle modification (low carb diet)

Metformin therapy with lifestyle modification

Other

Case #2

A 40 year old presents for routine biometric screening. BMI is 34& fasting glucose is 112 with an LDL of 134. He is currently a smoker & both his parents died from diabetes complications in their 50s. What would you do?

Begin Bariatric Surgery program/Intensive Lifestyle Modifications

Low Glucose Diet

Chantix for Smoking Cessation

Begin Statin or Metformin

Other

Case #2 continuedThe same 40 year old presents for routine biometric screening 3 years later. BMI is greater than 40 & fasting glucose is now 120 with an LDL of 194. He is still a smoker & both his parents died from diabetes complications in their 50s. What would you do?

Begin Bariatric Surgery program/Intensive Lifestyle Modifications

Low Glucose Diet

Chantix for Smoking Cessation

Begin Statin or Metformin

Other

Case #3

A 28 year old comes in for an annual physical looking to establish a primary care doctor. She has significant concern about her future health – notably diabetes. Her best friend has been struggling with brittle type 1 diabetes and her neighbors are uncontrolled type 2 diabetics. Her screening labs are unremarkable, BMI is less than 25, and blood pressure is at goal. What do you recommend?

Tell her not to worry about diabetes

Talk about mediterranean diet or other healthy diet choices

Emphasize preventive care, routine screenings, and discuss factors that would increase her risk

Application to Population Health

Challenge for population health is risk stratification.

This is primary purpose of biometric screenings

Next challenge is an intervention that a patient can actually achieve

7% weight loss and 150 minutes of exercise is not feasible for everyone

How to identify who is mostly likely to succeed

Finding other methods to reduce risk more effectively

Pitfalls of Population Health

Doing what’s best for the patient, not the data

Early adoption of new medication classes:

DPP-4

GLP-1

SGLT-2

Population Health Concerns

There is significant variability in how to utilize data

There are people from numerous points of view using this data in different ways

Statistics can be made to say anything

Individual clinician patient populations are not comparable (n size is not high enough)

Where population health is going; what the motivations are; and what we can do to help steer the ship so it doesn’t sink

ReferencesNathan DM, Berkwits M. Trials that matter: rosiglitazone, ramipril, and the prevention of type 2 diabetes. Ann Intern Med 2007; 146:461.

Naci H, Ioannidis JP. Comparative effectiveness of exercise and drug interventions on mortality outcomes: metaepidemiological study. BMJ 2013; 347:f5577.

Gillett M, Royle P, Snaith A, et al. Non-pharmacological interventions to reduce the risk of diabetes in people with impaired glucose regulation: a systematic review and economic evaluation. Health Technol Assess 2012; 16:1.

Selph S, Dana T, Blazina I, et al. Screening for type 2 diabetes mellitus: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med 2015; 162:765.

Balk EM, Earley A, Raman G, et al. Combined Diet and Physical Activity Promotion Programs to Prevent Type 2 Diabetes Among Persons at Increased Risk: A Systematic Review for the Community Preventive Services Task Force. Ann Intern Med 2015.

Tinker LF, Bonds DE, Margolis KL, et al. Low-fat dietary pattern and risk of treated diabetes mellitus in postmenopausal women: the Women's Health Initiative randomized controlled dietary modification trial. Arch Intern Med 2008; 168:1500.

Salas-Salvadó J, Bulló M, Babio N, et al. Reduction in the incidence of type 2 diabetes with the Mediterranean diet: results of the PREDIMED-Reus nutrition intervention randomized trial. Diabetes Care 2011; 34:14.

ReferencesSalas-Salvadó J, Bulló M, Estruch R, et al. Prevention of diabetes with Mediterranean diets: a subgroup analysis of a randomized trial. Ann Intern Med 2014; 160:1.

Estruch R, Ros E, Salas-Salvadó J, et al. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med 2013; 368:1279.

Bennett PH. Epidemiology of diabetes mellitus. In: Ellenberg and Rifkin's Diabetes Mellitus, Rifkin H, Porte D Jr (Eds), Elsevier, New York 1990. p.363.

Collins VR, Dowse GK, Toelupe PM, et al. Increasing prevalence of NIDDM in the Pacific island population of Western Samoa over a 13-year period. Diabetes Care 1994; 17:288.

Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346:393.

Nield L, Summerbell CD, Hooper L, et al. Dietary advice for the prevention of type 2 diabetes mellitus in adults. Cochrane Database Syst Rev 2008; :CD005102.

Mculloch et al., Prevention of Type 2 Diabetes Mellitus. UpToDate. July 2015.