Blood Glucose & Insulin Resistance · 1 week profiling Dietitian compiled 4–6 isocaloricoptions for each meal Good Diet Bad Diet Good Diet Bad Diet 1 week of each diet ... Lunch

Blood Glucose & Insulin Resistance

Barr et al., Diabetologia, 2009, Mar;52(3):415-24

All-

cau

se m

orta

lity

ra

te

(per

1,0

00 p

.y)

Fasting Glucose (mmol/L)

< 5.1 ≥ 5.1 ≥ 5.3 ≥ 5.6 ≥ 6.1 ≥ 7.0

5

10

25

All-

cau

se m

ort

ali

ty r

ate

(p

er 1

,000

p.y

)

Glucose Tolerance – 2h PG (mmol/L)

< 4.8 ≥ 4.8 ≥ 5.6 ≥ 6.3 ≥ 7.8 ≥ 11.1

5

10

25


All-

cau

se m

ort

ali

ty r

ate

(p

er 1

,000

p.y

)

HbA1C (%)

< 4.9 ≥ 4.9 ≥ 5.0 ≥ 5.2 ≥ 5.4

5

10

25


Image from: Kim et al., J Korean Endocr Soc. 2009 Jun;24(2):75-83

Measurement of Insulin Sensitivity

• At present, hyperinsulinemic euglycemic clamp and intravenous glucose tolerance test are the most reliable methods available for estimating insulin resistance [1]

• Hyperinsulinemic euglycemic clamp = “gold standard”

• Various indices of insulin sensitivity/resistance using the data from oral glucose tolerance test (OGTT): e.g. homeostasis model assessment (HOMA), quantitative insulin sensitivity check index (QUICKI)

• Fasting insulin alone was as accurate at predicting insulin resistance in the normoglycemic population as HOMA, insulin-to-glucose ratio, and the Bennett index [2]

[1] Gutch et al., Indian J Endocrinol Metab. 2015 Jan-Feb; 19(1): 160–164

[2] McAuley et al., Diabetes Care 2001 Mar; 24(3): 460-464

Image from Diabetes Ireland

Insulin Resistance – Practical Strategies

Wing et al., Diabetes Care. 2011 Jul; 34(7): 1481–1486

Cha

ng

e in

Hb

A1c

(%)

-0.6

-1

- 0.2

Wing et al., Diabetes Care. 2011 Jul; 34(7): 1481–1486

Cha

ng

e in

Fa

stin

g G

luco

se (

mg

/dl)

-30

-50

- 10

~ 800 kcal formula

~ 300 people with T2DM, BMI > 27, from 49 primary care practices

Best Practice Care

Lean et al., Lancet. 2018 Feb 10;391(10120):541-551

825-853 kcal diet for 3 months (up to 5)

Gradual food reintroduction (2–8 weeks)

Structured support for long-term weight loss maintenance

DiRECT Trial



Remission of diabetes: HbA1c less than 6·5% (<48 mmol/mol) after at least 2 months offall antidiabetic medications


Exercise

Peri-Workout

Pre-Loading

Circadian Rhythms

CHO Timing

Carbohydrate

Supplementation

Exercise

Peri-Workout

Pre-Loading

Circadian Rhythms

CHO Timing

Carbohydrate Low to moderate intake, high fibre

Supplementation

Exercise tl;dr = exercise is good

Peri-Workout

Pre-Loading

Circadian Rhythms

CHO Timing

Carbohydrate

Supplementation[1] Richter & Hargreaves, Physiol Rev. 2013 Jul;93(3):993-1017

[2] Duncan et al., Diabetes Care March 2003 vol. 26 no. 3 557-562

Exercise

Peri-Workout Bias carbohydrates here

Pre-Loading

Circadian Rhythms

CHO Timing

Carbohydrate

Supplementation

Exercise

Peri-Workout

Pre-Loading Protein or fibre/vegetables

Circadian Rhythms

CHO Timing

Carbohydrate:

Supplementation[1] Shukla et al., Diabetes Obes Metab. 2019 Feb;21(2):377-381

[2] Jakubowicz et al., Diabetologia. 2014 Sep;57(9):1807-11

[3] Frid et al., Am Jour Clin Nutr, Vol 82, Issue 1, 2005, pg 69–75

Exercise

Peri-Workout

Pre-Loading

Circadian Rhythms Alignment > Misalignment

CHO Timing

Carbohydrate:

Supplementation

Exercise

Peri-Workout

Pre-Loading

Circadian Rhythms

CHO Timing Carbs biased to earlier in the day

Carbohydrate:

Supplementation

Exercise

Peri-Workout

Pre-Loading

Circadian Rhythms

CHO Timing

Carbohydrate:

Supplementation a) Berberine

[1] Pérez-Rubio et al., Metab Syndr Relat Disord. 2013 Oct;11(5):366-9

[2] Dong et al., Evid Based Complement Alternat Med. 2012;2012:591654[3]

1,000 – 2,000 mg/d

Divided into 3 – 4 doses

High doses can lead to GI distress

Possible drug interactions

Exercise

Peri-Workout

Pre-Loading

Circadian Rhythms

CHO Timing

Carbohydrate:

Supplementation a) Berberine; b) Resistant Starch (10 – 45 g)

Wang et al., Nutrition & Diabetes (2019), vol 9, no. 19∆ Fasting glucose

R.S.

Wang et al., Nutrition & Diabetes (2019), vol 9, no. 19∆ Fasting insulin

Prebiotic Fiber

Raw: 8.6%

Cooked: 5%

17.5%

11.7%

5%1%

Exercise

Peri-Workout

Pre-Loading

Circadian Rhythms

CHO Timing

Carbohydrate:

Supplementation a) Berberine; b) Resistant Starch; c) Inositol?

Personalized Nutrition: The Future?

n = 800

Gut Microbiome Blood Tests Questionnaires Anthropometrics

Zeevi et al., Cell, Nov 2015, Volume 163, Issue 5, p1079–1094

Food Diary CGM

Day 1 Day 3 Day 5 Day 7

G F

Day 2 Day 4 Day 6

50 gCHO


Time

Glu

cose

(m

g/d

l)

160

120

80

08:00 12:00 16:00 20:00

2-hour PPGR AUC

Standardized meal

Lunch

Snack

Dinner


Zeevi et al., Cell, Nov 2015, Volume 163, Issue 5, p1079–1094Time

Bloo

d G

luco

se (

mg

/dl)

)

120

40

160

200

240

20 12060 80 100

Participant 67 – Test 1

Participant 67 – Test 2

Participant 358 - Test 1

Mean iAUC = 139

Mean iAUC = 15

Participant 358 - Test 2


PPGR - AUC (mg/dl/h)

Freq

uen

cy (

# p

art

icip

an

ts)

20

20

40

60

80

060400

85

Time (minutes)

Bloo

d G

luco

se (

mg

/dl)

Banana

Cookies

100

115

85

100

115Participant 445

Participant 644

0 120


Meal Carbohydrates (g)

PP

Glu

cose

Res

pon

se (

AUC)


25

Participant 49

Participant 14575

50

603015 45

PPGRs to the standardized meals (all types) positively associated with:

• HbA1c

• BMI

• Systolic blood pressure

• Alanine aminotransferase (ALT) activity

• CRP

Meal Response Predictor

Decision Tree XYZ

Meal Response Prediction20

BMI > 25 ?

Carbs > 10 g?N

250 5 30

Y

N

N

Y

YN

Firmicutes > 5% ?

Y

HbA1c > 5.7% ?

X 4,000

Main Cohortn = 800

Validation Cohortn = 100

Use meal response data to train the meal response predictor

algorithm

Validate meal response predictor

Intervention Trialn = 26

Test impact of “personalized nutrition” interventions

26 independent participants

12 14

1 week profiling

Dietitian compiled 4–6 isocaloric options for each meal

Good Diet Bad Diet Good Diet Bad Diet

1 week of each diet

Prediction Algorithm Expert Selection

Day 1 2 3 4 5 6

Breakfast B1 B2 B3 B4 B5 B6

Lunch L1 L2 L3 L4 L5 L6

Snack S1 S2 S3 S4 S5 S6

Dinner D1 D2 D3 D4 D5 D6

Low response High response

Dietitian prescribed meals

Day 1 2 3 4 5 6







Day 1 2 3 4 5 6







Time (days)

Blo

od G

luco

se (

mg

/dl)

Good Diet

Bad Diet

PPGR

iAU

C(m

g/d

l/h

)

Good Diet Bad Diet

Glu

cose

Flu

ctu

ati

on

s

Ma

x PP

GR iA

UC

(mg

/dl/

h)

0

80

40

0.2

120

60

Documents

Blood Glucose & Insulin Resistance · 1 week profiling Dietitian compiled 4–6 isocaloricoptions for each meal Good Diet Bad Diet Good Diet Bad Diet 1 week of each diet ... Lunch