type 2 diabetes mellitus - easo · obese people with prediabetes are at 17 times greater risk of...
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Type 2 Diabetes Mellitus
Volkan Demirhan Yumuk, MD
Diagnose Diabetes Mellitus
Obesity and diabetes syndemic
Define the potential complications of diabetes
Designing a treatment plan for people with obesity & type 2 DM
Learning objectives
Are you ready folks?
I have a case
Mr. Smith, a 52-year-old man, presents to you after a communityscreen reveals FBG 185mg/dl and HbA1c 7.9%. He has beenoverweight ever since but has gained more weight after the age of40. He has hypertension for 7 years and is on a beta blocker. Nohistory of coronary heart disease. His feet have been burning forabout a year. He is married and has 4 children. Drinks alcoholoccasionally and has never used tobacco. His father has type 2diabetes and mother has had CABG. He does office work andmoves only during lunch and coffee breaks. On weekends he isengaged in playing computer games with his son and watchingmovies at home with the family.
a. Quite normal
b. Impaired glucose tolerance
c. Impaired fasting glucose
d. Type 2 diabetes
e. Need to do OGTT
How do you interpret Mr. Smith’s FBG and A1c values?
FBG: 185 HbA1c: 7.9%
a. Quite normal
b. Impaired glucose tolerance
c. Impaired fasting glucose
d. Type 2 diabetes
e. Need to do OGTT
How do you interpret Mr. Smith’s FBG and A1c values?
Diagnosis of type 2 diabetes
Fasting plasma glucose
≥7.0 mmol/L(≥126 mg/dL)
2-hour post-challenge (OGTT) plasma glucose
≥11.1 mmol/L (≥200 mg/dL)
HbA1c
≥6.5%
All assessments were to be confirmed by repeated measurements
and/or
and/or
HbA1c, glycosylated haemoglobin; OGTT, oral glucose tolerance test.American Diabetes Association. Diabetes Care 2010;33(Suppl. 1):S11–61.
Obesity and Diabetes: A global syndemic
What is a syndemic?
Two or more epidemics interacting synergistically and
contributing as a result of their interaction to excess disease
burden in a population
Obese people with prediabetes are at 17 times greater risk of type 2 diabetes
*Prediabetes defined as fasting plasma glucose of 110 mg/dL (6.1 mmol/L) and 2-h plasma glucose less than 140 mg/dL (7.8 mmol/L); impaired glucose regulation: fasting plasma glucose
concentration 110–126 mg/dL (6.1–6.99 mmol/L) and/or 2-h plasma glucose concentration 140–200 mg/dL (7.8–11.09 mmol/L).
RR, relative risk; T2D, type 2 diabetes
RR f
or
T2D
vs.
healthy
subje
cts
Hu et al. Arch Intern Med 2004;164:892–6
Vital signs are unremarkable except for a BP of 150/100mmHg. Weight 130kg, height
178cm, Body Mass Index (BMI) is 41.0. His waist cicumference is 110 cm. No stigmata for
Cushing’s Syndrome. No facial or pretibial edema. There is loss of vibration bilaterally on
lower extremities assessed with a 128Hz tuning fork. The rest of the examination is
unremarkable.
Physical exam
FBG: 167mg/dl , 2hr. Post-prandial BG: 235mg/dl, HbA1c: 8.0%
Total kolesterol: 236mg/dl, Triglycerides: 250mg/dl
HDL-K: 30mg/dl, LDL-K:156mg/dl,VLDL-K: 50mg/dl
ALT: 75 IU/l, AST: 48 IU/l
Urinalysis: low grade albuminuria
Ultrasound upper abdomen: Grade 2 hepatosteatosis
Laboratory
1. Obesity
2. Type 2 diabetes
3. Hypertension
4. Hyperlipidemia
5. NAFLD
6. Peripheral diabetic neuropathy
Diagnoses
Obesity is associated with multiple chronic complications
Stroke
Type 2 diabetesPrediabetes
Coronary artery disease• Dyslipidaemia• Hypertension• LVH• CHF
Sleep apnoea
Pulmonary disease
GI diseases
Gynaecological abnormalitiesInfertility
Obesity contributes to 44% of the diabetes
burden3
77% of adults with obesity report some kind of sleep
problem4
Osteoarthritis
Non-alcoholic fatty liver disease
CHF = Congestive heart failure; GI = gastrointestinal; LVH = left ventricular hypertrophy.
1. NIH. Obes Res 1998;6 (Suppl 2):51S–209S; 2. Schelbert. Prim Care 2009;36:271–85; 3. WHO. Global health risks report 2009. Available at: http://www.who.int/healthinfo/global_burden_disease/global_health_risks/en/ 4. National Sleep Foundation. 2013 Sleep in America Poll. Available at: http://sleepfoundation.org/sleep-topics/obesity-and sleep/page/0%2C3/
a. Eye exam
b. Albumin creatinine ratio
c. Stress EKG
d. EMG
e. Chest X-ray
What other tests would you like to run on Mr. Smith in the first place?
a. Eye exam
b. Albumin creatinine ratio
c. Stress EKG
d. EMG
e. Chest X-ray
What other tests would you run on Mr. Smith in the first place?
Classification of Diabetic Retinopathy
Pre proliferative
• increased vascular permeability
• venous dilation
• Microaneurysms
• intraretinal hemorrhage
• Fluid leakage
• Retinal ischemia.
Proliferative
– Neovascularization
– Vitreous hemorrhage
– Fibrous proliferation (scarring).
Albuminuria
Urine on spot 24 hr urine
Albuminuria Albumin/creatinine
(mg/g)
UAE
(mg/day)
Normal <30 <30
Low grade 30-299 30-299
High grade >300 >300
Diabetes Care 2018
Peripheral neuropathy
Tuning fork 128Hz Esthesiometer 10g
a. Lifestyle modification
b. Pharmacotherapy
c. Bariatric/metabolic surgery
What is/are your treatment plan(s) for diabetes in Mr. Smith?
a. Lifestyle modification
b. Pharmacotherapy
c. Bariatric/metabolic surgery
What is/are your treatment plan(s) for diabetes in Mr. Smith?
EASO European guidelinesClinical care pathway for overweight and adults with obesity
Yumuk et al. Obes Facts. 2015;8:402-24.
Determine degree of overweight and obesity• Measure height (cm) and weight (kg) and calculate BMI (kg/m2)• Measure WC (cm)
If BMI ≥25 kg/m2* or WC ≥94 cm for men* or WC ≥80 cm for women*
AssessPresenting symptoms and underlying causes, comorbidities and health risks, weight loss history, lifestyle (nutrition and physical activity), eating behaviour, depression and mood disorders, chronic psychological stress, potential of weight loss to improve health, motivation to change, barriers to weight loss
Set goals and propose realistic, individualised and sustainable lifestyle changes at the long termWeight loss goal
5–15% of body weight or 0.5–1.0 kg/week
Management• Nutrition (reduce energy intake by 500-1000 kcal/day)• Physical activity (initially at least 150 min/week moderate aerobic exercise combined with 1–3 sessions/week
resistance exercise)• Cognitive behaviour therapy• Pharmacotherapy (BMI ≥30 kg/m2 or BMI ≥27 kg/m2 with comorbidities, adjunct to lifestyle modification)• Bariatric/metabolic surgery (BMI ≥40 kg/m2 or BMI between 35.0–39.9 kg/m2 + comorbidities or BMI between
30.0–34.9 kg/m2 with T2D on individual basis. Consider if other weight loss attempts fail; requires lifelong medical prevention)
• Prevention and treatment of comorbidities
Weight loss goal is achieved
Assess effect on comorbidities, weight maintenance and weight regain• Regular monitoring of weight, BMI and WC• Reinforce lifestyle modification• Address other risk factors
Consider referring to obesity specialist services or Collaborating Centres for Obesity Management • If the person has complex disease states or needs that can
not be managed in primary or secondary care• If the underlying causes of obesity need to be assessed• If conventional treatment has failed• If specialist interventions are needed• If bariatric/metabolic surgery is needed
*BMI and WC cut-off points are different for some ethnic groups. T2D, type 2 diabetes; WC, waist circumference
Anti-obesity drugs
Management & outcome
Reduction in CV mortality2
Improvements in blood lipid profile3
Improvements in blood pressure4
Benefits of 5–10% weight loss
Reduction in risk of type 2 diabetes1
Improvements in health-related quality
of life7,8
1. Knowler et al. N Engl J Med 2002;346:393–403; 2. Li et al. Lancet Diabetes Endocrinol 2014;2:474–80; 3. Datillo et al. Am J Clin Nutr 1992;56:320–8; 4. Wing et al. Diabetes Care 2011;34:1481–6; 5. Foster et al. Arch Intern Med 2009;169:1619–26; 6. Kuna et al. Sleep 2013;36:641–9; 7. Warkentin et al. Obes Rev 2014;15:169–82; 8. Wright et al. J Health Psychol 2013;18:574–86
Improvements in severity of
obstructive sleep aponea5,6
5% wt loss 11% wt loss 16% wt loss
Intrahepatic triglyceride content √ √ √ √ √ √Intra-abdominal adipose tissue √ √ √ √ √ √Adipose tissue insulin sensitivity √ √ √Liver insulin sensitivity √ √ √Muscle insulin sensitivity √ √ √ √ √ √Βeta cell function √ √ √ √ √ √Adipose tissue biology* √ √ √Inflammatory markers √ √ √
Weight loss has dose & tissue dependant biological effects
*Upregulation of genes involved in cholesterol flux,downregulation of genes involved in lipid synthesis,extracellular matrix remodelling & oxidative stress
Magkos F et al. Cell Metab. 2016 Apr 12;23(4):591-601.
a. Metformin
b. Sulphonylureas
c. DPP-4 inhibitors
d. Alpha-1 glycosidase inhibitors
e. Glinides
f. Thiozolidindiones
g. GLP-1 analogues
h. SGLTP-2 inhibitors
i. Insulin
What is/are your anti-diabetic drug choice(s) for Mr. Smith?
a. Metformin
b. Sulphonylureas
c. DPP-4 inhibitors
d. Alpha-1 glycosidase inhibitors
e. Glinides
f. Thiazolidindiones
g. GLP-1 analogues
h. SGLTP-2 inhibitors
i. Insulin
What is/are your anti-diabetic drug choice(s) for Mr. Smith?
ADA 2019
a. ACEIs or ARBs
b. Aspirin
c. Statins
d. Pregabalin or duloxetine
Other medications Mr. Smith may need for treatment of
complications of obesity and diabetes?
a. ACEIs or ARBs
b. Aspirin
c. Statins
d. Pregabalin or duloxetine
Other medications Mr. Smith may need for treatment of
complications of obesity and diabetes?
Recommendations: Hypertension/ Blood Pressure Treatment
Treatment for hypertension should include A
– ACE inhibitor
– Angiotensin II receptor blocker (ARB)
– Thiazide-like diuretic
– Dihydropyridine calcium channel blockers
American Diabetes Association Standards of Medical Care in Diabetes. Cardiovascular disease and risk management. Diabetes Care 2017; 40 (Suppl. 1): S75-S87
Recommendations: Diabetic Kidney Disease
In nonpregnant patients with diabetes and hypertension, either an ACE inhibitor or ARB is recommended for those with modestly elevated urinary albumin excretion (30–299 mg/g creatinine) B and is strongly recommended for patients w/ urinary albumin excretion ≥300 mg/g creatinine and/or eGFR <60. A
American Diabetes Association Standards of Medical Care in Diabetes.
Microvascular complications and foot care. Diabetes Care 2017; 40 (Suppl. 1): S88-S98
Recommendations: Antiplatelet Agents
Consider aspirin therapy (75–162 mg/day) C
As a primary prevention strategy in those with type 1 or type 2 diabetes at increased
cardiovascular risk
Use aspirin therapy (75–162 mg/day) as secondary prevention in those with diabetes and history of ASCVD. A
For patients w/ ASCVD & aspirin allergy, clopidogrel (75 mg/day) should be used. B
Dual antiplatelet therapy is reasonable for up to a year after an acute coronary syndrome. B
American Diabetes Association Standards of Medical Care in Diabetes. Cardiovascular disease and risk management. Diabetes Care 2017; 40 (Suppl. 1): S75-S87
Either pregabalin or duloxetine are recommended as initial pharmacologic treatments for neuropathic pain in diabetes. A
Management : Neuropathy
American Diabetes Association Standards of Medical Care in Diabetes. Microvascular complications and foot care. Diabetes Care 2017; 40 (Suppl. 1): S88-S98
Common bariatric surgery procedures
1. Field BC et al. Nat Rev Endocrinol 2010;6:444–53; 2. Lodhia NA et al. Int J Obes 2012;2:S47‒50;3. Mechanick JI et al. Obes (Silver Spring) 2013;21(Suppl 1):S1–27
Silicone band is placed around proximal stomach outlet to restrict
food intakeRestrictive
Stomach is constructed into a thin tube and most of the greater curvature of the stomach is
removedRestrictive
Small pouch is created from the stomach and connected to the
small intestine
Restrictive + malabsorptive
Procedure1 Type2,3
Adjustablegastricbanding
Sleevegastrectomy
Roux-en-Ygastricbypass
Description2,3
Patients in age groups from 18 to 60 years:
With BMI ≥ 40 kg/m2
With BMI 35–40 kg/m2 with co-morbidities in which surgically induced weight loss isexpected to improve the disorder (such as metabolic disorders, cardiorespiratory disease, severe joint disease, obesity-related severe psychological problems)
Patients with BMI ≥ 30 and < 35 kg/m2 with T2DM may be considered for bariatric surgery on an individual basis, as there is evidence-based data supporting bariatric surgery benefits in regards to T2DM remission or improvement
Indications for bariatric surgery
European Guidelines on Metabolic and Bariatric Surgery
Sjöström L. J Intern Med 2013; 273: 219-234.
3.year1 5.year2
Intensive Medical Therapy: %5 0
Sleeve Gastrectomy: %24 %15
RYGB : %38 %22
RYGB-IMT (P=0.002), SG-IMT (P=0.002)
1Schauer PR et al. STAMPEDE. NEJM 2014; 2Schauer PR et al. STAMPEDE. NEJM 2017.
Take home messages
• Obesity and type 2 diabetes are a global syndemic
• Obesity management is crucial in prevention and treatment of type 2 diabetes and its
complications
• Lifestyle modification, pharmacotherapy and metabolic surgery are the current treatment
choices
Evidence Grading System