Abordaje terapeutico del paciente con diabetes y obesidad · obstructive sleep apnea...

Abordaje terapeutico del paciente

con diabetes y obesidad

Barto Burguera MD, PhDProfessor of Medicine Director of Obesity ProgramsEndocrinology and Bariatric InstitutesCleveland Clinic Lerner College of Medicine of [email protected]

Learning Objectives

Obesity: severity of the problem

Weight gain and development of diabetes

Therapeutic tools to treat Obesity

Weight loss as therapeutic tool to treat diabetes

Retinopathy

Neuropathy

Nephropathy

CAD

Diabetes

Obeso

Diabetes

Hypertension

Dislipemia

CAD

International Diabetes Federation, 2003.NAASO. Arch Intern Med 2000;160:898–904Ng M. et al Lancet Published online May 29, 2014

• In Western countries, nearly 90% of T2DM cases can be attributed to weight gain

• Two-thirds of adults diagnosed with T2D have a BMI of ≥27 kg/m2

Medical Complications of Obesity

Phlebitisvenous stasis

Coronary heart disease

Pulmonary diseaseabnormal functionobstructive sleep apneahypoventilation syndrome

Gallstones

Gout

Diabetes

Osteoarthritis

Fatty liver diseasesteatosissteatohepatitiscirrhosis

Hypertension

Dyslipidemia

Cataracts

Skin disorders

Pancreatitis

Intracranial hypertensionCognitive dysfunction

Cancerbreast, uterus, cervix, ovary, prostate, kidney, colon, Esophagus, pancreas, gallbladder, liver

Gynecologic abnormalitiesabnormal mensesinfertilitypolycystic ovarian syndrome

Stroke

Patients are concerned about weight gain: questions posted on diabetes web forums

• “I’ve heard that once you control blood sugar you gain weight?”

• “Is it true that insulin causes weight gain? I would have hoped to lose weight”

• “Since starting on insulin 8 months ago, I’ve gained 26 kg. I am so depressed. Are there other treatments I could try instead?”

• “I’ve tried hard to lose weight, but since starting insulin my weight has increased. I’m willing to be more strict with my diet but I worry that could cause hypoglycaemia….”

• “Are there any drugs for weight loss suitable for diabetics on insulin?

Key challenges of type 2 diabetes

1. Diabetes is a progressive disease characterized by:

– Declining beta-cell function– Deterioration of glycemic control– Microvascular complications– Increased risk of cardiovascular disease

1. As diabetes treatments are added to control glucose, physicians and patients frequently need to deal with:

– Increased risk of hypoglycaemia– Weight gain– Complex treatment regimens– Increased requirement for self monitoring

Is there any benefit for weight loss in T2DM?

Modest Weight Loss Has Benefits, with Greater Weight Loss Associated with Greater Benefit

• Measures of glycemia1

• Triglycerides1 and HDL cholesterol1

• Systolic and diastolic blood pressure• Hepatic steatosis measured by MRS2

• Measures of feeling and function:– Symptoms of urinary stress incontinence5

– Measures of sexual function6,7

– Quality of life measures (IWQOL)8

• NASH Activity Score measured on biopsy3

• Apnea-hypopnea index4

• Reduction in CV events, mortality, remission T2DM9

1. Wing et al. Diabetes Care 2011;34:1481-14862. Lazo et al. Diabetes Care 2010;33:2156–21633. Promrat et al. Hepatology 2010;51:121–1294. Foster et al. Arch Intern Med 2009;169:1619–1626

5. Phelan et al. Urol. 2012;187:939-944 6. Wing et al. Diab Care 2013;36:2937-29447. Wing et al. Journal of Sexual Medicine 2010 ; 7:156-658. Crosby, Manual for the IWQOL-LITE Measure9. Eliasson B, Lancet Diabetes Endocrinol 2015;3(11): 847–54.

-3.0%

-5.0%

-10.0%

-15.0%

ObesityPrimary Problem

Medications

Diabetes Treatment

•Lifestyle Modification

•Drug Therapy:

– >85% suffer obesity

– Obesity treatment useful approach?

HISTORY OF PRESENT ILLNESS:

• Mary K is a 48 year old female who is presenting on July 16, 2015 for weight management

• History of bipolar disorder x 19 years.

• History of obesity. Since age 18. Pretty much overweight since high school

– Portion sizes, medications, eating too much fat and sugar, emotional eating and lack of physical activity have been major

continuing factors to her weight gain

• Hx of prediabetes x 1 year. Currently treated with life style intervention and metformin 500 mg bid.

• She did not tolerate higher doses due to GI side effects

• Monitors her BG qw. Glucose readings in AM~ 110s w/o evidence of hypoglycemias

• Glucose control has slowly deteriorated over the last few months; hemoglobin A1c increased from 5.8 6.1%

• 10 pound weight loss

• Taking several medications associated to weight gain such as Latuda, Lithium, neurontin and trazodone.

History

• Diet: Her breakfast consists of hot cereal or Greek yogurt or shake with fruits and spinach

• Lunch she has several slices bread with ham and cheese and mayonnaise or a homemade turkey

• Dinner she usually has chicken, spinach salad and a small potato

• She drinks water and coffee.

• Her level of physical activity is limited: she walks once a week for a period of 20 minutes

• Her appetite is not well controlled. She is pretty much hungry all the time

• She does not sleep well usually less than 7 hours. There is no evidence of obstructive sleep apnea

• Her level of stress is 6/10. She is frustrated/depressed with her weight and her general health status

REVIEW OF SYSTEMS:

• WEIGHT: decreased 10 lb.

• Fatigue.

• EYES: Normal

• HYDRATION: no thirst and polydipsia.

• CARDIAC: no chest pain, dyspnea, palpitations or edema

• GI: no nausea, fullness, vomiting, diarrhea, constipation, GI bleeding or heartburn

• GU: nocturia

• SEXUAL/REPRODUCTIVE: normal. IUD.

• SKIN: normal

• MUSCULO-SKELETAL: Joint pain both knee(s) and Back pain.

• NERVOUS SYSTEM: no numbness, paresthesias, weakness, cramping, burning or dizziness

• PSYCH: depression. History of bipolar disorder. History of alcohol abuse in the past.

PAST MEDICAL HISTORY

• Bipolar Affective (Hcc) - 1988

• Psoriasis - 1989

• Psoriatic Arthritis (Hcc) - 1992

• Stiff-Man Syndrome - 2008

• Plantar Fasciitis

• Alcohol Dependence, in Remission

• Asthma

• Allergic Rhinitis, Cause Unspecified (Allergic rhinitis)

• Hepatitis (nonspecific)

• Lower Leg Dvt (Deep Venous Thrombosis) (Hcc) - 2004 (one in each leg)

• Tendonitis of Ankle - 7/17/2013

• History of prediabetes

• Hx of hypothyroidism.

• Morbid Obesity

Results for as of 7/18/2015 10:29AM

Ref. Range 11/20/2014 15:18 1/8/2015 15:18 6/12/2015 12:49

• Hemoglobin A1C Latest Range: 4.0-6.0 % 5.8 6.1 (H)

• Free T4 Latest Range: 0.7-1.8 ng/dL 1.3

• TSH Latest Range: 0.400-5.500 uU/mL 2.820

• Vitamin D 25 Hydroxy Latest Range: 31.0-80.0 ng/mL 22.1 (L)

SOCIAL HISTORY

• Lives in a nursing home. Her mother is here with her today

• Employer And Job Title: No employer specified (nanny)

• Years Of Education Completed: 14 years

• Marital Status: Unknown with no children

• Tobacco Use: 1 packs/day, for 30 years. Quit 01/01/2008. Types: Cigarettes

• Alcohol Use: No (sober 9 years)

• Drug Use: No (quit years ago "everything but crack and heroin")

• Sexual Activity: Patient is not presently sexually active.

Current outpatient prescriptions:

• loratadine (CLARITIN) 10 mg tablet Take 1 tablet by mouth once daily.

• gabapentin (NEURONTIN) 300 mg capsule 300 mg in am and pm, 600 mg at night (total daily 1200)

• Metformin (glucophage) 500 mg tablet Take 1 tablet by mouth once a daily.

• blood sugar diagnostic (ACCU-CHEK SMARTVIEW TEST STRIP) test strip Daily or Use as instructed

• Lancets (ACCU-CHEK FASTCLIX) lancets Daily or Use as instructed

• apremilast (OTEZLA) 30 mg tablet Take 30 mg by mouth twice daily.

• traZODone (DESYREL) 100 mg tablet Take 100 mg by mouth daily at bedtime.

• levothyroxine (SYNTHROID) 88 mcg tablet Take 1 tablet by mouth daily before breakfast.

• topiramate (TOPAMAX) 100 mg tablet Take 100 mg by mouth once daily.

• LAMOTRIGINE 200 mg tablet Take 200 mg by mouth once daily.

• lurasidone (LATUDA) 80 mg ORAL tablet Take 80 mg by mouth once daily.

• lithium CR 450 mg ORAL CR tablet Take 1 tablet by mouth twice daily.

PHYSICAL EXAM:

• BP 155/84 | Pulse 71 | Ht 157.5 cm (5' 2") | Wt 104.101 kg (229 lb 8 oz)

• Body mass index is 41.97 kg/(m^2).

• Appearance Well appearing, alert, in no acute distress, well-hydrated, well nourished., obese

• Eyes PERRLA, conjunctiva and sclera normal

• Neck Supple, no adenopathy; thyroid symmetric, normal size, no bruits

• Heart RRR with normal S1 and S2, no murmurs, no gallops, no JVD appreciated

• Lungs clear to auscultation

• Abd bowel sounds normoactive, no bruits, soft, non-tender, non-distended, without organomegaly

• Extremities Normal, No deformities, No skin discoloration, No edema and Normal pulses bilaterally.

• Feet: No foot lesion

• Neuro Awake, alert and oriented x 3, No involuntary motions. and Reflexes symmetrical

• Skin Color, texture, turgor normal. No rashes or lesions

Impression and plan: Mary K is a very pleasant 48 year old female with hx of:

Impression and plan: Mary K is a very pleasant 48 y.o. female with hx of:

1.- Prediabetes for the last year. She is not compliant

It is going to get worse

• Her HgA1c is at 6.1%.

• Suboptimal eating habits (Nursing home)

• Limited exercise

• Poor sleeping higiene

• Follow-up with endocrine.

• Add SU, DDP4-inh or Glitazone for the time being?

2.- Morbid obesity. This patient's BMI is 42.

• Referral to the bariatric Institute ASAP.

3.- History of bipolar disease: follow-up with psychiatry.

4.- Stiff man syndrome. Follow up with neurology.

Follow-up in 6 months.

Dietician.

Level 4.

Impression and plan: Mary Lou is a very pleasant 48 years old y.o.

female with hx of:

1.- Prediabetes for the last year. She is not compliant

• It s going to get worse

• Her HgA1c is at 6.1%.

• Suboptimal eating habits (Nursing home)

• Limited exercise


• Follow-up with endocrine.

• Add SU or Glitazone for the time being?


• Referral to the bariatric Institute ASAP.

3.- History of bipolar disease: follow-up with

psychiatry.

4.- stiff man syndrome. Follow up with neurology.

Follow-up in 6 months.

Dietician.

Level 4.


• Starting on lifestyle intervention program involving improvement of diet, a personalized

exercise program and the possibility of using medications to control her appetite

• She will also follow-up with dietitian

• Exercise program

• We need to control her appetite

• Consider starting appetite suppressants

2.- History of bipolar disease: follow-up with psychiatry

• Topamax as per her neurologist Some of the other antipsychotics that she is taking

increased appetite.

• Talk to her psychiatrist regarding anti-psych meds

3.- Prediabetes for the last year.

• Her HgA1c is at 6.1%. Aggressive LSI will prevent development of diabetes

• She is willing to try to walk 20 min bid. -> Exercise Physiologist

• She should monitor her BG qw. F/u Ophthalm f/u q/yr

• We will also check HgA1c in 3 months.

• Not tolerating metformin GLP-1 analog (or sGLUT-2 inh)– Vicotza 0.6 mg 1.8 mg sc qd

• RTC in 1 month after above consults obtained

• Level 5

Follow-up when we treat the Diabetes

1.- Prediabetes for the last year. She is more compliant.

Patient is being followed by endocrinology

She stopped taking metformin GI SE

Started on Amaryl 2 md bid

• Her HgA1c is at 6.1% 5.9%.

2.- Morbid obesity. This patient's BMI is 42 44

Patient was not a good surgical candidate due to her bipolar disease


4.- Stiff man syndrome. Follow up with neurology

Follow-up in 6 months PRN

Patient stopped taking metformin GI SE and started on Amaryl 2 md bid

Patient continues to be frustrated. Psychiatry follow-up.

Continues to eat poorly and she does not exercise.

She has developed obstructive sleep apnea problems with C-pap

Increased joint pain

Follow-up: when we treat the Obesity

• .- DMT2 for the last year. She is more compliant.

• Patient is being followed by endocrinology.

She stop taking metformin GI SE

Started on Amaryl 2 md bid

• Her HgA1c is at 6.4% 5.9%.

• Continues to eat poorly and she does not

exercise.


• 2.- Morbid obesity. This patient's BMI is 42 44.

• Patient was not a good surgical candidate due to

her bipolar disease.

• 3.- History of bipolar disease: follow-up with

psychiatry.

• 4.- stiff man syndrome. Follow up with neurology.

• Follow-up in 6 months PRN.

• 1.- Morbid obesity. This patient's BMI was 42

• Lifestyle intervention program: improvement of diet, exercise program

• Exercise program

• Follow-up with dietitian

• Medications to reduce appetite

• On Topamax as per her neurologist.


• Off Trazadone and Latuda. Cont. with Lithium

• Started on Wellbutrin. Close f/u by Psych

• 2.- Prediabetes for the last year.

• HgA1c is at 6.1%. 5.9%

• Walking 60 min qd. -> Exercise Physiologist

• Victoza 1.8 mg sc qd

• She should monitor her BG bid. F/u Ophthalm f/u q/yr.

• We will also check HgA1c in 2 months.

This patient's BMI was 42 29.7

(14 months later)

Patient is taking metformin 500 mg after dinner.

Victoza 1.8 mg subcutaneous once a day.

Exercise program. Follow-up with dietitian.

On Topamax as per her neurologist.

Off Trazadone and Latuda. Cont. with Lithium. Wellbutrin recently added.

Close f/u with psychiatry and psychology.

Follow up.

50 year old female who originally presented on July 16, 2015 for diabetes

management and today she is here for follow-up. (1-17-2017)

In our first visit we outlined a lifestyle intervention program involving a personalized dietary program, we optimized her level of

physical activity, provide her with an exercise program and optimized her T2D therapy

• She is happy with the progress obtained over the last few weeks

• Aerobic exercising 4-5 days per week. Water exercises and weights

• She is having problems with her nutrition at her nursing home Eating more carbs over the holidays

• She does not sleep well usually less than 7 hours. There is no evidence of obstructive sleep apnea.

• She is very proud of her accomplishment. She has lost 85 pounds

• History of type 2 diabetes and we have treated her with metformin 500 mg bid and also Victoza 1.8 mg sc once a day.

• In spite of that weight loss and surprisingly her hemoglobin A1c has increased up to 12.7% (10.1---> 7.2%-->12.7).

• Given this circumstance she was started on Lantus 10 un by her PCP. She did not tolerate Invokana due to vaginal yeast

infection.

• Her blood sugars have been in the 150s-240. The blood glucose readings are getting better now that she has become more

physically active.

Mary Kay is a very pleasant 50 year old yo female with hx of:

Impression and plan:

1.- DMT2 for the last year. Her metabolic profile has significantly improved with weight loss

Her HgA1c was at 10.7--> 7.3-->12.3%.

She will continue with swimming pool twice a week and also walk on a daily basis

She will continue with Victoza at a dose of 1.8 mg and 500 mg of metformin bid

She will increase Lantus to 14 un.

Letter to NH asking for a low carb diet

She did not tolerate Invokana 100 mg qd.

She needs Ophthalm f/u q/yr.

We will also check HgA1c in 3 months.

2.- Morbid obesity. This patient's BMI is 42-->39-->37.8.-->36.8-->35-->33.1--> 30.3. Patient has responded extremely well to a lifestyle

intervention program involving improvement of her diet, a personalized exercise program

She seems to be doing quite well with Victoza.

Very important that she continues with an exercise program. She will also follow-up with dietitian.

She should continue to take Topamax as per her neurologist which is associated with decreased appetite.

History of bipolar disease. She is being followed by psychiatry. She has been able to taper the much all her medications. She is back on

Latuda.

Next visit in 12 week(s).

• This nice lady has a history of T2D and we have treated her with

– Metformin 500 mg bid

– Victoza 1.8 mg subcutaneous once a day

– Lantus 12 u qhs. She is doing very well. She has lost 85 pounds.

• In spite of that weight loss and surprisingly her hemoglobin A1c

had increased up to 12.7%

• Eating much healthier at the NH and more active

• HgA1c has significantly reduced to almost normal (10.1--->

7.2%-->12.7--> 7.4% today

Follow up.

50 year old female who originally presented on July 16, 2015 for

diabetes management and today she is here for follow-up. (4-11-2017)

• Impression and plan:

• Mary Kay Moore is a very pleasant 50 year old yo female with hx of:

• 1.- DMT2 for the last year. Her metabolic profile has significantly improved with weight loss

• Her HgA1c was at 10.7--> 7.3-->12.3--> 7.4%.

• She will continue with swimming pool twice a week and also walk on a daily basis

• She will continue with Victoza at a dose of 1.8 mg and try to increase to 1000 mg of metformin twice a day.

• She will reduce Lantus to 12 un.

• 2.- Morbid obesity. This patient's BMI is 42-->39-->37.8.-->36.8-->35-->33.1--> 29.5

• Patient has responded extremely well to a lifestyle intervention program involving improvement of her diet, a personalized exercise program and medications to

control her appetite. She seems to be doing quite well with Victoza.

• Very important that she continues with an exercise program. She will also follow-up with dietitian.

• She should continue to take Topamax as per her neurologist which is associated with decreased appetite.

• History of bipolar disease. She is being followed by psychiatry.

• Next visit in 12 week(s).

A1C 6.5 – 7.5%**

Monotherapy

MET +

GLP-1 or DPP4 1

TZD 2

Glinide or SU 5

TZD + GLP-1 or DPP4 1

MET +Colesevelam

AGI 3

2 - 3 Mos.***

2 - 3 Mos.***

2 - 3 Mos.***

Dual Therapy

MET +

GLP-1 or

DPP4 1+

TZD 2

Glinide or SU 4,7

A1C > 9.0%

No Symptoms

Drug Naive Under Treatment

INSULIN

± Other

Agent(s) 6

Symptoms

INSULIN

± Other

Agent(s) 6

INSULIN

± Other

Agent(s) 6

Triple Therapy

AACE/ACE Algorithm for Glycemic

Control Committee

Cochairpersons:

Helena W. Rodbard, MD, FACP, MACE

Paul S. Jellinger, MD, MACE

Zachary T. Bloomgarden, MD, FACE

Jaime A. Davidson, MD, FACP, MACE

Daniel Einhorn, MD, FACP, FACE

Alan J. Garber, MD, PhD, FACE

James R. Gavin III, MD, PhD

George Grunberger, MD, FACP, FACE

Yehuda Handelsman, MD, FACP, FACE

Edward S. Horton, MD, FACE

Harold Lebovitz, MD, FACE

Philip Levy, MD, MACE

Etie S. Moghissi, MD, FACP, FACE

Stanley S. Schwartz, MD, FACE

* May not be appropriate for all patients

** For patients with diabetes and A1C < 6.5%, pharmacologic Rx may be considered

*** If A1C goal not achieved safely

† Preferred initial agent

1 DPP4 if PPG and FPG or GLP-1 if PPG

2 TZD if metabolic syndrome and/or

nonalcoholic fatty liver disease (NAFLD)

3 AGI if PPG

4 Glinide if PPG or SU if FPG

5 Low-dose secretagogue recommended

6 a) Discontinue insulin secretagogue

with multidose insulin b) Can use pramlintide with prandial insulin

7 Decrease secretagogue by 50% when added to GLP-1 or DPP-4

8 If A1C < 8.5%, combination Rx with agents

that cause hypoglycemia should be used with caution

9 If A1C > 8.5%, in patients on Dual Therapy,

insulin should be considered

MET +

GLP-1

or DPP4 1 ± SU 7

TZD 2

GLP-1

or DPP4 1± TZD 2

A1C 7.6 – 9.0%

Dual Therapy 8

2 - 3 Mos.***

2 - 3 Mos.***

Triple Therapy 9

INSULIN

± Other

Agent(s) 6

MET +

GLP-1 or DPP4 1

or TZD 2

SU or Glinide 4,5

MET +

GLP-1

or DPP4 1+ TZD 2

GLP-1

or DPP4 1 + SU 7

TZD 2

MET † DPP4 1 GLP-1 TZD 2 AGI 3

Available at www.aace.com/pub

© AACE December 2009 Update. May not be reproduced in any form without express written permission from AACE

• Foto DC

48 y.o. patient: CC obesity and diabetes

• Obese “all his life”

• Multiple diets and weight-loss programs: PSMF, WW, …

– Weight regained

• Very little exercise due to knee pain and “lack of time”

• Always tired and almost fell asleep on his job

• Anesthesiologist

• Stressful schedule

• Night shift. Poor sleeping

• He skips meals frequently: snacking

• Meds: Omeprazol

• Insulin Lantus 10 un AM, Novolog 10 un tid, Actos 30 mg.

• Atenolol 50 mg

• Simvastatin: 40 mg, Ezetimibe 10mg

• Adiro 100 mg, Prozac 20 mg

• Weight: 120.4 kg (265 lb) ht: 175.3 cm (5' 9") BMI: 39.2 kg/m2

Waist: 130 cm (51”) BP: 145/95 mm hg. Pulse: 80

• PE:

– Acanthosis nigricans. No goiter

– Abd: Striae < 1cm. Trace edema

WEIGHT GAIN ASSOCIATED WITH USE ALTERNATIVES(WEIGHT REDUCING IN

PARENTHESES)*

Insulin (weight gain differs with type and regimen used)

Sulfonylureas Thiazolidinediones Sitagliptin? Metiglinide

(Metformin) (Acarbose) (Miglitol) (Pramlintide) (Exenatide) (Liraglutide)(sGLT-2 inh).

Medications for Diabetes and Weight

Apovian CM, Aronne LJ, Bessesen DH et al. Pharmacologic Management of obesity: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2015 doi:10.1210/jc.2014-3415

* Only liraglutide 3.0 is FDA-approved for chronic weight management in patients with BMI 30+ kg/m2 or BMI 27 <30 kg/m2 with one or more comorbidities.

Diabetes therapy:

Glucocentric VS.

• Pt with T2DM.

– Obesity is a complication

Adipocentric

• Pt with Obesity and comorbidities:

– T2DM

– HTA

– OA

– OSA

– GERD

– Fatty Liver

Diabetes therapy:

Glucocentric VS.

• Pt with T2DM. Obesity complication

• Therapeutic target: HgA1c

Adipocentric

• Pt with Obesity and comorb:T2DM

47

Glucose control gets worse overtime

UKPDS 34. Lancet 1998:352:854–865; Kahn et al, (ADOPT), NEJM 2006;355(23):2427-43

6.2% – upper limit of normal range

8.0

6.0

7.5

7.0

6.5

Time (years)

0

0 2 3 4 51

Rosiglitazone vs Metformin–0.13 (–0.22 to –0.05), P=0.002

Rosiglitazone vs Glibenclamide–0.42 (–0.50 to –0.33), P<0.001

ADOPT

6

7

8

9

Med

ian

Hb

A1

c(%

)

Years from randomization

Conventional*

GlibenclamideMetforminInsulin

Recommended treatment

target ≤7.0†

2 4 6 8 100

UKPDS

7.5

8.5

6.5

*Diet initially then sulphonylureas, insulin and/or metformin if FPG > 15 mmol/l

†ADA clinical practice recommendations. n=5102

Metformin

Glibenclamide

Rosiglitazone

Diabetes therapy:

Glucocentric VS.


• Therapeutic target: HgA1c

Adipocentric


• Therapeutic target: BMI, abd. cc

Diabetes therapy:

Glucocentric VS.


• Therapeutic target HgA1c

• Most common therapies

Weight gain

• Based on UKPDS data

Adipocentric


• Therapeutic target: BMI, abd. Cc

Most therapies result in weight gain over time

Glibenclamide (n=277)

Years from randomisation

Insulin (n=409)

Metformin (n=342)

Conventional treatment (n=411); diet initially then sulphonylureas, insulin and/or metformin if FPG >15 mmol/L

UKPDS: up to 8 kg in 12 years ADOPT: up to 4.8 kg in 5 years

Weig

ht

(kg)

Rosiglitazone, 0.7 (0.6 to 0.8)Metformin, -0.3 (-0.4 to -0.2)**Glibenclamide, -0.2 (-0.3 to 0.0)**

Change in w

eig

ht

(kg)

0

1

5

0 3 6 9 12

8

7

6

4

3

2

Years

0 1 2 3 4 5

96

92

88

0

100

UKPDS 34. Lancet 1998:352:854–65. n=at baseline; Kahn et al (ADOPT). NEJM 2006;355(23):2427–43

Diabetes therapy:

Glucocentric VS.



• Most common therapies >weight


Adipocentric



• Wt loss improves all CVRs (T2DM)

• Based on Look –AHEAD and

Stampede studies

Changes in Weight, Physical Fitness, Waist Circumference, and Glycated Hemoglobin Levels during 10 Years of Follow-up.

The Look AHEAD Research Group. N Engl J Med 2013;369:145-154

Mean Changes in Measures of Diabetes Control from Baseline to 3 Years.

Schauer PR et al. N Engl J Med 2014;370:2002-2013

Diabetes therapy:

Glucocentric VS.





• 8 therapeutic classes to treat T2DM

• Acceptable Insurance coverage

Adipocentric




• Based on Look –AHEAD and GBPS

Agent A1c Advantages Disadvantages Cost

SUs 1–2% Microvasc risk Hypo, wt gain, -cell exhaust

$

‘Glinides 1–1.5% PPG Hypo, wt gain, -cell exhaust, dose frequency

$ $ $

Biguanides 1–2% Wt loss, no hypo, CVD, ? malignancy

GI, lactic acidosis B12-deficiency

$

TZDs 1–1.5% No hypo; -cell preservTG HDL BP ? CVD (pio)

Wt gain, edema / HF Bone fxs, ? CVD (rosi)

$ $ $

-GIs 0.5–1% PPG, ? CVD; GI, dose frequency $ $

GLP-1 R agonists

1% Wt loss,? -cell preserv, ? CV benefits

GI; ? pancreatitis, injections

$ $ $

Amylino-mimetics

0.5% Wt loss, PPG GI, dose frequency, injections

$ $ $

DPP-4 inhibitors

0.6–0.8% No hypo Urticaria / Angioedema; ? pancreatitis

$ $ $

Bile acid sequestrants

0.5% No hypo; LDL-C GI; TGs $ $ $

D2 agonists 0.5% No hypo Nausea; dizziness $ $ $

T2DM: Therapeutic Landscape (Noninsulin) 2012

Inzucchi SE et al. Diabetes Care 2012;35:1364-1379.

Diabetes therapy:

Glucocentric VS.







Adipocentric





• Five meds to treat obesity

• Very poor insurance coverage

Medications approved for chronic weight management and how they workhttp://www.accessdata.fda.gov/scripts/cder/drugsatfda/http://www.accessdata.fda.gov/scripts/cder/drugsatfda/.

ER: extended release; SR: sustained release. 5HT: serotonin. GABA: Gamma aminobutyric acid. GLP-1: Glucagon-like peptide 1.

Agent Action ApprovalScheduled

Drug

Orlistat

Xenical®

• Peripheral pancreatic lipase inhibitor - blocks ingested fat absorption

Approved 1997 • No

LorcaserinBelviq®

• 5-HT2C serotonin agonist• Little affinity for other serotonergic

receptors

Approved 2012 • YES

Phentermine/ Topiramate ER Qsymia™

• Sympathomimetic• Anticonvulsant (GABA receptor

modulator, carbonic anhydrase inhibitor, glutamate antagonist)

Approved2012 • YES

Naltrexone SR/ Bupropion SRContrave®

• Opioid receptor antagonist• Dopamine/noradrenaline reuptake

inhibitor

Approved2014 • No

Liraglutide 3.0 mgSaxenda®

• GLP-1 receptor agonist Approved2014 • No

Diabetes therapy:

Glucocentric VS..







• All algorithms are GLUCOCENTRIC

Adipocentric




• Based on Look –AHEAD and

GBPS



Diabetes therapy:

Glucocentric VS.







• All algorithms are GLUCOCENTRIC

Adipocentric







• Adipocentric algorithms are starting

Therapeutic algorithm for patientswith obesity and type 2 DM

Burguera B, Khawla F. Ali, Brito JP Antiobesity drugs in the management of type 2 diabetes:A shift in thinking? Clev Clin J Med. In press. July 2017

Changes in treatment:

• Slowly taper insulin

– Short acting first

• Stop Actos (or SU)

• Add metformin

• Add sGLT2 inh

• Consider also a GLP-1 analog

• An optimal approach to type 2 DM:

– control of glycemia and its associated comorbidities

• Obesity a key player

• Many of our first-line oral treatments for type 2 DM are

associated with weight gain

• Worsen control of glycemia insulin further exacerbating

therapy the weight gain

• It seems counterintuitive to treat a disease for which

obesity is one of the main risk factors, with

medications that promote weight gain

Approach to patient with obesity and Diabetes:

• Concentrating in the main problem: the obesity

• Treat the disease while we address the comorbidities

• Detailed medical history: Precipitating factors?

– physical activity, nutrition

– sleep, stress– depression–anxiety

• Look at the medications

• Identified colleagues who can help you:

– nutrition–exercise physiologist–sleep specialists

• Patient needs support, knowledge and tools

• Close follow-up.

• Consider shared medical appointments

• No hay excusa para no hacer acitividad fisica!

An intensive life-style program, offered to patients with severe obesity, who are not candidates or

not interested in undergoing bariatric surgery.

In the context of Shared Medical Appointments.

Team: Dietician, Nurse, Endocrinologist, Exercise Physiologist, Psychologist, and Surgeon

Endocrinology Institute and DDI (Bariatric Institute Institute).

Objective: To develop an optimal medical weight loss program to offer patients with BMI > 35

non-surgical candidates.

It is our goal to accomplish 5-10% weight after 12 months of intervention and weight loss

maintenance after 36 months.

T2DM: 25%

Program is now included in CCF Health Plan.

Cleveland Clinic Integrated Medical

Weight Management Program

We provide tools Accountability

1.- Nutrition: quality, quantity, portion sizes, drinks …

2.- Physical Activity: personalized exercise programs.

GOALS: short and midterm

3.- Appetite control: weight loss medications

4.- Sleep patterns. R/o OSA

5.- Stress. Depression. Anxiety

Bariatric surgery, if a medical approach is not successful

Emphasis on :

APPETITE

REGULATION

ADIPOSTAT: SET POINT

DIET PH ACTIVITY STRESS SLEEP

GI

signals

GI

FLORA

LIGHTFAT

signals

APPETITE

REGULATION

VITAMINS

MEDICATIONS

BARIATRIC SURGERYADIPOSTAT: SET POINT

Phases of Obesity Treatment

Phase I(Weight Loss)

3-6 months

Phase II(Weight-Loss Maintenance)

Indefinitely

When you stop treatment,

the disease comes back!

Weig

ht

PA compensates for the reduction in EE that occurs with weight loss and reduces the degree of caloric restriction required to stay in energy balance at a reduced body weightTo stay in energy balance at a reduced body weight, EI must decrease or EE must increase permanently from the pre-weight loss state

Energy Gap

Abordaje terapeutico del paciente con diabetes y obesidad · obstructive sleep apnea...

Documents

Transcript of Abordaje terapeutico del paciente con diabetes y obesidad · obstructive sleep apnea...