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Reversing the Rising Tide of Type 2 Diabetes in Nova Scotia with Therapeutic Nutrition Michael Mindrum, MD, FRCPC Assistant Professor, Dalhousie University Department of Internal Medicine Dalhousie Fall Refresher November 2019 Slide set for web-posting

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Page 1: Reversing the Rising Tide of Type 2 Diabetes in Nova ... · Reaven, Peter D, Nicholas V Emanuele, Wyndy L Wiitala, Gideon D Bahn, Domenic J Reda, Madeline McCarren, William C Duckworth,

Reversing the Rising Tide of Type 2 Diabetes in Nova Scotia with Therapeutic Nutrition

Michael Mindrum, MD, FRCPCAssistant Professor, Dalhousie University

Department of Internal MedicineDalhousie Fall Refresher

November 2019Slide set for web-posting

Page 2: Reversing the Rising Tide of Type 2 Diabetes in Nova ... · Reaven, Peter D, Nicholas V Emanuele, Wyndy L Wiitala, Gideon D Bahn, Domenic J Reda, Madeline McCarren, William C Duckworth,

DISCLOSURES

Position & Organization DetailsMember of Expert Advisory CommitteeInstitute for Personalized Therapeutic Nutrition (not-for-profit)

https://www.therapeuticnutrition.org/

Medical DirectorValley Metabolic Program

Utilizes carbohydrate restriction for patients with types 2 diabetes and metabolic disease.

Grant Money (2017) Valley Regional Hospital Foundation

Initiated a program for carbohydrate restriction for patients with type 2 diabetes.

ParticipantUBC/IPTN physician feasibility study

Testing an online platform, GroHealth, to deliver therapeutic carbohydrate restriction.

No conflicts of interest with pharmaceutical companies or industry.

Michael Mindrum, MD, FRCPCAssistant Professor, Dalhousie University

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Objectives

Part 1: Setting the Stage

Epidemiology and natural history of type 2 diabetes

Limitations of our conventional approach to treatment

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Objectives

Part 2: The Evidence

Physiologic models of type 2 diabetes remission

Review the evidence for therapeutic nutrition

Consider effectiveness of low carbohydrate diets

Page 5: Reversing the Rising Tide of Type 2 Diabetes in Nova ... · Reaven, Peter D, Nicholas V Emanuele, Wyndy L Wiitala, Gideon D Bahn, Domenic J Reda, Madeline McCarren, William C Duckworth,

https://www.canada.ca/en/public-health/services/chronic-diseases/reports-publications/diabetes/diabetes-canada-facts-figures-a-public-health-perspective/chapter-1.html; *2017 curve generated from 2016/2017 diabetes prevalence from Nova Scotia DCPNS registry data

Age

Prev

alan

ceType 2 diabetes prevalence:

a rising tide

10 35 5545 65 75 8525

2000

2005

2009

15

30

0

Turin TC, Saad N, Jun M, et al. Lifetime risk of diabetes among First Nations and non-First Nations people. CMAJ. 2016; 188(16):1147-53. .

2017*

1999

20

25

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Rodgers, A., Woodward, A., Swinburn, B., & Dietz, W. H. (2018). Comment Prevalence trends tell us what did not precipitate the US obesity epidemic. The Lancet Public Health, 3(4), e162–e163. http://doi.org/10.1016/S2468-2667(18)30021-5

Obe

sity

Pre

vale

nce

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Adiposity and Type 2 DM

Healthy fat cells

Over-filled & inflamed

somatic fat cells

Spill over of fat into visceral organs

Pre-DM T2D

For further reference review “twin cycle hypothesis” see: Taylor, R., Al-Mrabeh, A., Endocrinology, N. S. T. L. D., 2019. (n.d.). Understanding the mechanisms of reversal of type 2 diabetes. Elsevier

“personal fat threshold”

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Natural History of Type 2 Diabetesand our conventional approach to treatment

UKPDS

SU/InsulinSU/Insulin

Figure courtesy of CADRE. Adapted from Holman RR. Diabetes Res Clin Pract. 1998, 40 (suppl) S1-S25; Ramlo-Halsted BA, Edelman SV. Prim Care 1999; 26: 771-789; Nathan DM N Eng J Med. 2002; 347:1342–1349; UKPDS Group. Diabetes 1995: 44: 1249-1258; Figure adapted by MMindrum from American Association of Clinical Endocrinologists: https://www.aace.com/;

ACCORD ADVANCE

VADT

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Limitations to Conventional Approach: ACCORD TRIAL

Outcome Event Rate (Annual) RRR ARR Time(yrs)

NNH95% CIIntensive Standard

MACE 2.11% 2.29% N/A N/A 3.5

n/aMortality 1.41% 1.14% -23.6% -0.24% NNH of 95Hypoglycemia 10.5% 3.5% -45% -7% NNH of 14

ACCORD Study Group, William C Cushman, Gregory W Evans, Robert P Byington, David C Goff, Richard H Grimm, Jeffrey A Cutler, et al. “Effects of Intensive Blood-Pressure Control in Type 2 Diabetes Mellitus.” New England Journal of Medicine 362, no. 17 (April 29, 2010): 1575–85. https://doi.org/10.1056/NEJMoa1001286.

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Limitations to Conventional Approach:VADT Trial 15 yr follow up

”There was no evidence of a legacy effect or a mortality benefit with intensive glucose control.”

Reaven, Peter D, Nicholas V Emanuele, Wyndy L Wiitala, Gideon D Bahn, Domenic J Reda, Madeline McCarren, William C Duckworth, Rodney A Hayward, and VADT Investigators. “Intensive Glucose Control in Patients with Type 2 Diabetes - 15-Year Follow-Up.” New England Journal of Medicine 380, no. 23 (June 6, 2019): 2215–24. https://doi.org/10.1056/NEJMoa1806802.

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CADTH Network Meta-Analysis, comparative effectiveness

DrugClass

A1c Weight(kg)

Systolic BP

OR of severe

hypo-glycemia

OR of

SAEs

OR of withdrawal

DPP4 i -0.58 0.18 -1.04 0.91 0.91 0.78

GLP-1a -0.88 -1.44 -2.79 1.8 1.05 1.8

SGLT-2 -0.67 -2.21 -4.06 0.61 1.11 1

SUs -0.7 2.11 0.28 6.4 0.96 0.74

Basal Insulin

-0.85 2.76 1 3 1.48 0.33

Therapeutics Review Recommendations; 2017 (4): 1 - 20

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Individualizing A1C Targets

Consider 7.1-8.5% if:

UKPDSACCORD ADVANCEVADT

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Limitations to Our Conventional Approach

“Current evidence supports that there is a potential epidemic in the overtreatment with antihyperglycemic therapies in

diabetes.”

Lipska, K. J., Ross, J. S., Miao, Y., Shah, N. D., Lee, S. J., & Steinman, M. A. (2015). Potential Overtreatment of Diabetes Mellitus in Older Adults With Tight Glycemic Control. JAMA Internal Medicine, 175(3), 356–7. http://doi.org/10.1001/jamainternmed.2014.7345

Makam AN, Nguyen OK. An evidence-based medicine approach to antihyperglycemic therapy in diabetes mellitus to overcome overtreatment. Circulation. 2017; 135(2):180-95. DOI: 10.1161/CIRCULATIONAHA.116.022622

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Nolan, Christopher J., Neil B. Ruderman, Steven E. Kahn, Oluf Pedersen, and Marc Prentki. “Insulin Resistance as a Physiological Defense Against Metabolic Stress: Implications for the Management of Subsets of Type 2 Diabetes.” Diabetes 64, no. 3 (March 2015): 673–86. https://doi.org/10.2337/db14-0694.

Limitations to Our Conventional Approach

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Nolan, Christopher J., Neil B. Ruderman, Steven E. Kahn, Oluf Pedersen, and Marc Prentki. “Insulin Resistance as a Physiological Defense Against Metabolic Stress: Implications for the Management of Subsets of Type 2 Diabetes.” Diabetes 64, no. 3 (March 2015): 673–86. https://doi.org/10.2337/db14-0694.

Approach to Treatment

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Part 2: Diabetes Reversal & Remission

Long Term Complications of diabetes mellitus. DM Nathan NEJM (1993).328(23), 1676–1685. http://doi.org/10.1056/NEJM199306103282306

Turner, R. C., Cull, C. A., Frighi, V., & Holman, R. R. (1999). Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. Jama, 281(21), 2005–2012.

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Therapeutic Nutrition

Individually tailored intervention designed to manage or reverse patient specific metabolic dysfunctions, medical

conditions, or their associated symptoms.

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Kahneman, D. (2011). Thinking, fast and slow. New York: Farrar, Straus and Giroux

Cognitive Bias

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Type 2 diabetes reversal

Healthy fat cells

Over-filled & inflamed

somatic fat cells

Spill over of fat into visceral organs

Pre-DM T2D

For further details see “twin cycle hypothesis” by Taylor, R., Al-Mrabeh, A., Endocrinology, N. S. T. L. D., 2019. (n.d.). Understanding the mechanisms of reversal of type 2 diabetes. Elsevier

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Dietary TrialsNatural history of type 2 diabetes

;

VIRTADiRECT VMP

50% decline in beta-cell function

Figure courtesy of CADRE. Adapted from Holman RR. Diabetes Res Clin Pract. 1998, 40 (suppl) S1-S25; Ramlo-Halsted BA, Edelman SV. Prim Care 1999; 26: 771-789; Nathan DM N Eng J Med. 2002; 347:1342–1349; UKPDS Group. Diabetes 1995: 44: 1249-1258; Figure adapted by MMindrum from American Association of Clinical Endocrinologists: https://www.aace.com/; modified by MMINDRUM to include dietary trials

Look AHEAD

JAMAPREDIMED

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Macronutrients

carbohydrates

plant-based protein vs.animal based protein

SaturatedMono-unsaturated

Poly-unsaturated fats

fats

Page 22: Reversing the Rising Tide of Type 2 Diabetes in Nova ... · Reaven, Peter D, Nicholas V Emanuele, Wyndy L Wiitala, Gideon D Bahn, Domenic J Reda, Madeline McCarren, William C Duckworth,

Low Fat

plant based protein >animal based

carbohydrates

fats

Page 23: Reversing the Rising Tide of Type 2 Diabetes in Nova ... · Reaven, Peter D, Nicholas V Emanuele, Wyndy L Wiitala, Gideon D Bahn, Domenic J Reda, Madeline McCarren, William C Duckworth,

Mediterranean

carbohydrates

plant-based protein &high fish intake

High MUFA

fats

Page 24: Reversing the Rising Tide of Type 2 Diabetes in Nova ... · Reaven, Peter D, Nicholas V Emanuele, Wyndy L Wiitala, Gideon D Bahn, Domenic J Reda, Madeline McCarren, William C Duckworth,

Low Carbohydrate

animal based protein or plant based protein

carbohydrates

fats

Page 25: Reversing the Rising Tide of Type 2 Diabetes in Nova ... · Reaven, Peter D, Nicholas V Emanuele, Wyndy L Wiitala, Gideon D Bahn, Domenic J Reda, Madeline McCarren, William C Duckworth,

Low Energy

carbohydrates

Protein

fats

Page 26: Reversing the Rising Tide of Type 2 Diabetes in Nova ... · Reaven, Peter D, Nicholas V Emanuele, Wyndy L Wiitala, Gideon D Bahn, Domenic J Reda, Madeline McCarren, William C Duckworth,

Diabetes Remission

Term DefinitionPartial A1c < 6.5 off medicationsComplete A1c < 5.7 off medicationsProlonged Complete remission > 5 yrs (cure)

Alternate DefinitionReversal A1c <6.5 without medication beside metformin (Virta) Remission A1c < 6.5 off all medications for at least 2 months (DiRECT)

Buse, J. B., Caprio, S., Cefalu, W. T., Ceriello, A., Del Prato, S., Inzucchi, S. E., et al. (2009). How Do We Define Cure of Diabetes? Diabetes Care, 32(11), 2133–2135.

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Look AHEAD

⚫ Randomized 5145 patients with obesity & T2D to intensive lifestyle intervention or control designed to generate modest weight loss.

⚫ Intensive Lifestyle Intervention utilizing meal replacement systems and healthy low fat diet (<30% fat).⚫ Weekly group and individual counseling for 6 months⚫ Then 3 sessions per month for 6 months⚫ Then twice monthly for 4 yrs

⚫ Control arm coached for healthy low fat diet and 3 group sessions per year

⚫ Post hoc analysis looked at partial or complete remission of T2D defined as an A1c <6.5 without diabetes medications

Gregg, E. W., Chen, H., Wagenknecht, L. E., Clark, J. M., Delahanty, L. M., Bantle, J., et al. (2012). Association of an Intensive Lifestyle Intervention With Remission of Type 2 Diabetes. Jama, 308(23), 2489–8.

The Look AHEAD Research Group. (2013). Cardiovascular Effects of Intensive Lifestyle Intervention in Type 2 Diabetes. New England Journal of Medicine, 369(2), 145–154.

The Look AHEAD Research Group. (2014). Eight-year weight losses with an intensive lifestyle intervention: The look AHEAD study. Obesity, 22(1), 5–13.

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Look AHEAD: Prevalence of Complete or Partial Remission

Gregg, E. W., Chen, H., Wagenknecht, L. E., Clark, J. M., Delahanty, L. M., Bantle, J., et al. (2012). Association of an Intensive Lifestyle Intervention With Remission of Type 2 Diabetes. Jama, 308(23), 2489–8. http://doi.org/10.1001/jama.2012.67929

8 KG 5 KG

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Look AHEAD: Durability of partial or complete remission

Gregg, E. W., Chen, H., Wagenknecht, L. E., Clark, J. M., Delahanty, L. M., Bantle, J., et al. (2012). Association of an Intensive Lifestyle Intervention With Remission of Type 2 Diabetes. Jama, 308(23), 2489–8. http://doi.org/10.1001/jama.2012.67929

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Figure adapted from American Association of Clinical Endocrinologists: https://www.aace.com/;

Look AHEADlow durability of remission

Perhaps modest results are due to intervening too late or a different intervention is needed?

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• The 7 year cumulative incidence of achieving any remission was 1.6% among >100,000 patients

• Conclusion: Type 2 DM remission using dietary guidelines from the ADA with a calorie restricted <30% dietary fat can happen, but it is very rare.

• Difference between efficacy (Look AHEAD) and effectiveness.

• Could we do better with a different dietary strategy?

Page 32: Reversing the Rising Tide of Type 2 Diabetes in Nova ... · Reaven, Peter D, Nicholas V Emanuele, Wyndy L Wiitala, Gideon D Bahn, Domenic J Reda, Madeline McCarren, William C Duckworth,

Direct Trial: A Low Energy Dietary Intervention

⚫ Open label, cluster randomized trial, 49 primary care practices in Scotland & England

⚫ 149 intervention participants age 20 to 65, T2D < 6 yrs

⚫ Intervention with ~850 kcal/day formula for 3 to 5 months followed by stepped food reintroduction over 2 to 8 weeks & structured supports for weight loss maintenance (monthly visits) & “rescue plan” of 2 to 4 weeks partial meal replacement if weight regain occurs.

⚫ Withdrawal of medications for blood sugar and blood pressure medications

⚫ Those on insulin were excluded

⚫ Primary outcome at one year⚫ Weight loss >15 kg⚫ A1c < 6.5 for 2 months off all anti-diabetes medications

Lean, M. E., Leslie, W. S., Barnes, A. C., Brosnahan, N., Thom, G., McCombie, L., et al. (2018). Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. The Lancet, 391(10120), 541–551. http://doi.org/10.1016/S0140-6736(17)33102-1

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DiRECT Trial T2D Remission

Lean, M. E., Leslie, W. S., Barnes, A. C., Brosnahan, N., Thom, G., McCombie, L., et al. (2018). Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. The Lancet, 391(10120), 541–551. http://doi.org/10.1016/S0140-6736(17)33102-1

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DiRECT Trial: T2D remission & weight loss

Lean, M. E., Leslie, W. S., Barnes, A. C., Brosnahan, N., Thom, G., McCombie, L., et al. (2018). Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. The Lancet, 391(10120), 541–551. http://doi.org/10.1016/S0140-6736(17)33102-1

*Look Ahead at one year had 11% remission rate with 8 kg weight loss

Page 35: Reversing the Rising Tide of Type 2 Diabetes in Nova ... · Reaven, Peter D, Nicholas V Emanuele, Wyndy L Wiitala, Gideon D Bahn, Domenic J Reda, Madeline McCarren, William C Duckworth,

Meta-Analysis of Weight Loss (LCHF vs Low Fat)

Hall, K. D., & Guo, J. (2017). Obesity Energetics: Body Weight Regulation and the Effects of Diet Composition. Gastroenterology, 152(7), 1718–1727.e3.

Page 36: Reversing the Rising Tide of Type 2 Diabetes in Nova ... · Reaven, Peter D, Nicholas V Emanuele, Wyndy L Wiitala, Gideon D Bahn, Domenic J Reda, Madeline McCarren, William C Duckworth,

Common Ground:Limit Ultra-Processed Foods

Hall, K. D., Ayuketah, A., Brychta, R., Cai, H., Cassimatis, T., Chen, K. Y., et al. (2019). Ultra-Processed Diets Cause Excess Calorie Intake and Weight Gain: An Inpatient Randomized Controlled Trial of Ad Libitum Food Intake. Cell Metabolism, 1–61.

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Key Points

Structured supports are key.

Modest changes lead to modest results.

If possible, act early.

Enthusiasm for remission can be tempered by duration of diabetes and intensity of lifestyle change.

Restricting fat or carbohydrates provides similar weight loss.

Page 38: Reversing the Rising Tide of Type 2 Diabetes in Nova ... · Reaven, Peter D, Nicholas V Emanuele, Wyndy L Wiitala, Gideon D Bahn, Domenic J Reda, Madeline McCarren, William C Duckworth,

Carbohydrate RestrictionGlucose variability independent of weight loss

Gannon, M. C., Hoover, H., & Nuttall, F. Q. (2010). Further decrease in glycated hemoglobin following ingestion of a LoBAG30 diet for 10 weeks compared to 5 weeks in people with untreated type 2 diabetes. Nutrition & Metabolism,

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Page 40: Reversing the Rising Tide of Type 2 Diabetes in Nova ... · Reaven, Peter D, Nicholas V Emanuele, Wyndy L Wiitala, Gideon D Bahn, Domenic J Reda, Madeline McCarren, William C Duckworth,

Carbohydrate RestrictionDiet Grams of CHO / day StudyVery low carbohydrate ketogenic diet

<30 VIRTAVMP

Low carbohydrate ketogenic diet

<50 JAMA

Liberal low carbohydrate diet

50 to 130 CSIRO

Moderate carbohydrate, calorie restricted

>130 (< 50% from CHO & > 30% from fat)

PREDIMED

Vegetables, whole grains, low in red meat, higher in poultry, fish, olive oil.

Photo courtesy of: www.dietdoctor.com

Page 41: Reversing the Rising Tide of Type 2 Diabetes in Nova ... · Reaven, Peter D, Nicholas V Emanuele, Wyndy L Wiitala, Gideon D Bahn, Domenic J Reda, Madeline McCarren, William C Duckworth,

PREDIMED

NEWLY diagnosed patients.

Randomized Mediterranean diet (108) or low fat diet (107)

Restrict energy to around 1500 kcal/day (women) and 1800 kcal/day (men)

Esposito, K., Maiorino, M. I., Petrizzo, M., Bellastella, G., & Giugliano, D. (2014). The effects of a Mediterranean diet on the need for diabetes drugs and remission of newly diagnosed type 2 diabetes: follow-up of a randomized trial. Diabetes Care, 37(7), 1824–1830.

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PREDIMED:Prevalence of Remission

Esposito, K., Maiorino, M. I., Petrizzo, M., Bellastella, G., & Giugliano, D. (2014). The effects of a Mediterranean diet on the need for diabetes drugs and remission of newly diagnosed type 2 diabetes: follow-up of a randomized trial. Diabetes Care, 37(7), 1824–1830.

Page 43: Reversing the Rising Tide of Type 2 Diabetes in Nova ... · Reaven, Peter D, Nicholas V Emanuele, Wyndy L Wiitala, Gideon D Bahn, Domenic J Reda, Madeline McCarren, William C Duckworth,

Carbohydrate RestrictionDiet Grams of CHO / day StudyVery low carbohydrate ketogenic diet

<30 VIRTAVMP

Low carbohydrate ketogenic diet

<50 JAMA

Liberal low carbohydrate diet

50 to 130 g CSIRO

Moderate carbohydrate, calorie restricted

>130 g (< 50% from CHO & > 30% from fat)

PREDIMED

Less red meat and butter 🡪 more fish and olive oil to keep saturated fat similar to low fat diet

Photo courtesy of: www.dietdoctor.com

Page 44: Reversing the Rising Tide of Type 2 Diabetes in Nova ... · Reaven, Peter D, Nicholas V Emanuele, Wyndy L Wiitala, Gideon D Bahn, Domenic J Reda, Madeline McCarren, William C Duckworth,

CSIRO Trial

115 adults with T2D

Randomized to energy matched hypo-caloric diets for 2 yrs to LCHF vs low fat, each keeping saturated fat to <10%

Tay, J., Thompson, C. H., Luscombe-Marsh, N. D., Wycherley, T. P., Noakes, M., Buckley, J. D., et al. (2017). Effects of an energy-restricted low-carbohydrate, high unsaturated fat/low saturated fat diet versus a high-carbohydrate, low-fat diet in type 2 diabetes: A 2-year randomized clinical trial. Diabetes, Obesity and Metabolism, 20(4), 858–871. http://doi.org/10.1111/dom.13164

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Weight Hgb A1c

CSIRO Trial

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Medication Reduction Glucose Variability

CSIRO Trial

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Carbohydrate RestrictionDiet Grams of CHO / day StudyVery low carbohydrate ketogenic diet

<20 grams VIRTAVMP

Low carbohydrate ketogenic diet

<50 JAMA

Liberal low carbohydrate diet

50 to 130 g CSIRO

Moderate carbohydrate, calorie restricted

>130 g (< 50% from CHO & > 30% from fat)

Mediterranean

Photo courtesy of: www.dietdoctor.com

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JAMA

Yancy, William S., Matthew J. Crowley, Moahad S. Dar, Cynthia J. Coffman, Amy S. Jeffreys, Matthew L. Maciejewski, Corrine I. Voils, Anna Barton Bradley, and David Edelman. “Comparison of Group Medical Visits Combined With Intensive Weight Management vs Group Medical Visits Alone for Glycemia in Patients With Type 2 Diabetes: A Noninferiority Randomized Clinical Trial.” JAMA Internal Medicine, November 4, 2019. https://doi.org/10.1001/jamainternmed.2019.4802.

263 veterans with T2D

Randomized to LCHF (<50 g/day) vs conventional treatment with group medical visits every 8 weeks.

Can intervention lead to non-inferior A1c with less medications?

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Yancy, William S., Matthew J. Crowley, Moahad S. Dar, Cynthia J. Coffman, Amy S. Jeffreys, Matthew L. Maciejewski, Corrine I. Voils, Anna Barton Bradley, and David Edelman. “Comparison of Group Medical Visits Combined With Intensive Weight Management vs Group Medical Visits Alone for Glycemia in Patients With Type 2 Diabetes: A Noninferiority Randomized Clinical Trial.” JAMA Internal Medicine, November 4, 2019. https://doi.org/10.1001/jamainternmed.2019.4802.

JAMAA1c and Medication Reduction

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Carbohydrate RestrictionDiet Grams of CHO / day StudyVery low carbohydrate ketogenic diet

<20 grams VIRTAVMP

Low carbohydrate ketogenic diet

<50 JAMA

Liberal low carbohydrate diet

50 to 130 g CSIRO

Moderate carbohydrate, calorie restricted

>130 g (< 50% from CHO & > 30% from fat)

Mediterranean

Photo courtesy of: www.dietdoctor.com

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Virta Health Study

349 adults enrolled

Open label and non randomized comparing ketogenic diet versus usual care

Treatment arm also used remote monitoring and virtual care

Hallberg, S. et al. (2018). Effectiveness and Safety of a Novel Care Model for the Management of Type 2 Diabetes at 1 Year: An Open-Label, Non-Randomized, Controlled Study. Diabetes Therapy : Research, Treatment and Education of Diabetes and Related Disorders, 9(2), 583–612.

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Athinarayanan, S. J., Adams, R. N., Hallberg, S. J., McKenzie, A. L., Bhanpuri, N. H., Campbell, W. W., et al. (2019). Long-Term Effects of a Novel Continuous Remote Care Intervention Including Nutritional Ketosis for the Management of Type 2 Diabetes: A 2-Year Non-randomized Clinical Trial. Frontiers in Endocrinology, 10, 348. http://doi.org/10.3389/fendo.2019.00348

Virta Health Study

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Athinarayanan, S. J., Adams, R. N., Hallberg, S. J., McKenzie, A. L., Bhanpuri, N. H., Campbell, W. W., et al. (2019). Long-Term Effects of a Novel Continuous Remote Care Intervention Including Nutritional Ketosis for the Management of Type 2 Diabetes: A 2-Year Non-randomized Clinical Trial. Frontiers in Endocrinology, 10, 348. http://doi.org/10.3389/fendo.2019.00348

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Insulin Dosing

Athinarayanan, S. J., Adams, R. N., Hallberg, S. J., McKenzie, A. L., Bhanpuri, N. H., Campbell, W. W., et al. (2019). Long-Term Effects of a Novel Continuous Remote Care Intervention Including Nutritional Ketosis for the Management of Type 2 Diabetes: A 2-Year Non-randomized Clinical Trial. Frontiers in Endocrinology, 10, 348. http://doi.org/10.3389/fendo.2019.00348

Virta Health StudyInsulin Dosing

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Athinarayanan, S. J., Adams, R. N., Hallberg, S. J., McKenzie, A. L., Bhanpuri, N. H., Campbell, W. W., et al. (2019). Long-Term Effects of a Novel Continuous Remote Care Intervention Including Nutritional Ketosis for the Management of Type 2 Diabetes: A 2-Year Non-randomized Clinical Trial. Frontiers in Endocrinology, 10, 348. http://doi.org/10.3389/fendo.2019.00348

https://blog.virtahealth.com/2yr-t2d-trial-outcomes-virta-nutritional-ketosis/

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Athinarayanan, S. J., Adams, R. N., Hallberg, S. J., McKenzie, A. L., Bhanpuri, N. H., Campbell, W. W., et al. (2019). Long-Term Effects of a Novel Continuous Remote Care Intervention Including Nutritional Ketosis for the Management of Type 2 Diabetes: A 2-Year Non-randomized Clinical Trial. Frontiers in Endocrinology, 10, 348. http://doi.org/10.3389/fendo.2019.00348Table from https://blog.virtahealth.com/2yr-t2d-trial-outcomes-virta-nutritional-ketosis/

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Key PointsCarbohydrate restriction

Act early if possible.

The less the carbohydrate the more effective (modest changes lead to modest results).

Can achieve similar to better glycemic control on less medications.

Leads to improved glucose variability and less hypoglycemia.

Improvement in blood pressure and dyslipidemia.*

Interventions via IT platform/virtual care or group medical visits have shown to be effective.

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Valley Metabolic Program

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VMP Intervention

⚫ Offered teaching on why to consider carbohydrate restriction and how to do it

⚫ Valley Metabolic Guide Book

⚫ 5 Group sessions at 0, 2, 4, 8, 12 weeks

⚫ Grocery store tours

⚫ Health professional monitored FB page

⚫ Follow patients clinically for one year.

⚫ Can we improve A1c on less drug therapy with a low tech approach?

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VMP Participants

⚫ 35 patients

⚫ Average age 60

⚫ Average duration of T2D 12 years

⚫ 11 of 35 patients were on insulin (average duration 10 yrs)

⚫ Baseline A1c of 7.4

⚫ 25 patients returned for 1 year follow up, all data included

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Valley Metabolic ProgramQuality Improvement

12 month ResultsData analysis courtesy

Dr. Jonathon Little (PhD), and Helena Neudorf PhD(c)University of British Columbia

(unpublished)

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VMP One Year Overview

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Medication De-Prescribing

Adapted from: Murdoch, C., Unwin, D., Cavan, D., Cucuzzella, M., & Patel, M. (2019). Adapting diabetes medication for low carbohydrate management of type 2 diabetes: a practical guide. British Journal of General Practice, 69(684), 360–361. http://doi.org/10.3399/bjgp19X704525

Drug group Hypo Risk? SuggestionSulfonylureas Yes Reduce/stop (if gradual CHO

restriction wean by 50%)Insulins Yes Typically wean by 30 to 50%

successively depending on baseline glucose and CHO level*

SGLT2i No Stop. Risk of euglycemic DKABiguanides No Individualize, often maximizeDPP-4 No Individualize, consider stoppingGLP1a No Individualize.

Thiazidolones No Usually stopSuggest glucose target of 7 to 10 while weaning down on hypoglycemic agents of insulin or sulfonylurea. Consider diagnosis of LADA prior to de-prescribing insulin.

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A1c for Insulin Users

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A1c

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Key Point

Carbohydrate restriction is effective for patients in our community with achieving similar A1c with less drugs.

It is a refreshing clinical experience.

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Guidelines

⚫ 2018: ADA and EASD approved use of low carbohydrate diets as medical nutrition therapy for adults with type 2 diabetes.

⚫ Guidelines in the UK and Australia are also inclusive of carbohydrate restriction.

⚫ The UK and ADA recognize remission as an appropriate aim for type 2 DM management (bariatric surgery, low calorie, carbohydrate restriction).

⚫ Diabetes Canada: Macronutrient distribution is flexible within recommended ranges (45 to 65% CHO) and will depend on individual treatment goals and preferences. 😩😩😩

Diabetes Australia. Position Statement: Low carbohydrate eating for people with diabetes. 2018. Available from: https://static.diabetesaustralia.com.au/s/fileassets/diabetes-australia/8b4a8a54-f6b0-4ce6-bfc2-159686db7983.pdf. Diabetes UK. Position Statement: Low-carb diets for people with diabetes. 2017. Available from: www.diabetes.org.uk/professionals/positionstatements-reports/food-nutrition-lifestyle/lowcarb-diets-for-people-with-diabetes. Davies MJ, D’Alessio DA, Fradkin J, et al. Management of hyperglycemia in type 2 siabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2018;41(12):2669-2701.

Sievenpiper JL, Chan CB, Dworatzek PD, Freeze C, Williams SL. Diabetes Canada 2018 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada: Nutrition Therapy. Can J Diabetes 2018;42(Suppl 1):S64-S79.

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T2D management with therapeutic nutrition: don’t forget the other guidelines

Vasc

ular

Pro

tect

ion

Smoking Cessation

Blood Pressure Control

Often stop or decrease diuretics at start of diet

Liberalize salt intake

Reduce dosing if SBP <120 & hold if SBP <110, *Increase

salt intakeACE/ARBs

Glycemic Control

Relax glycemic control for de-prescribing hypoglycemic

agents

Recognize improved glycemic variability

Statins based on guideline targets

Diet, Exercise, Sleep,

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Optimism

Discussion