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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