Substituting a Type-4 Resistant Starch for Available Carbohydrate Reduces Postprandial Glucose, Insulin and Hunger: An Acute, Randomized, Double-Blind, Controlled Study

Substituting a Type-4 Resistant Starch for Available Carbohydrate Reduces Postprandial Glucose, Insulin and Hunger:  An Acute, Randomized, Double-Blind, Controlled Study1

 By Kristen N Smith, PhD, RD, LD; Mary R Dicklin, PhD; Kevin C Maki, PhD

 Background:

Dietary fiber (including a wide variety of nondigestible carbohydrates) is a noted shortfall nutrient in Western diets, despite the fact that appropriate consumption is associated with a broad range of health benefits.2,3 One of the benefits that has received considerable attention is blunting of postprandial blood glucose control. Researchers have established a benefit between consumption of viscous fibers and blood glucose excursions.4 When certain fibers, such as resistant starch (RS), are used in place of available carbohydrate in foods, less glucose is liberated through digestion, thus lowering the rate and quantity of glucose entering the bloodstream after a meal.5

It is important to note that there are different types of RS receiving varying levels of attention in clinical trials. These differences are outlined in the table below.

Type of RS

Description

Amount of Research

Resistant starch type-2

Granular, native starch

Resistant to digestion

Majority of clinical research is in these 2 areas

Resistant starch type-3

Retrograded starch

Resistant to digestion

Resistant starch type-4 (RS4)

Chemically modified starch

Resists digestion by intestinal enzymes

Fewer clinical trials in this area

Among the types of RS4, phosphate distarch phosphate is the most frequently tested6-8, with fewer studies on hydroxypropyl distarch phosphate9,10 and only one study on acid hydrolyzed and heat treated RS4, to date.11

The primary aim of this study was to characterize the postprandial blood glucose response in healthy adults to a novel RS4 (acid hydrolyzed and heat treated maize-based RS) in a ready-to-eat baked good (scone), compared with the response to consumption of a scone made with a control starch. The secondary aims were to evaluate postprandial insulin response, satiety and gastrointestinal tolerance. It was hypothesized that the replacement of digestible carbohydrate from refined wheat flour with RS4 would reduce postprandial blood glucose.

 Methods:

This was a double-blind, randomized, controlled trial conducted at MB Clinical Research in Boca Raton, Florida, USA.

Main Entry Criteria:

  • Age 18-74 y
  • Men and women
  • Body mass index (BMI) 18.5-29.99 kg/m2
  • General good health
  • Fasting capillary glucose <100 mg/dL

The treatment fiber scone contained VERSAFIBE™ 2470 resistant starch (provided by Ingredion Incorporated, Bridgewater, NJ) as the primary fiber source. VERSAFIBE™ 2470 is a RS4 with 70% dietary fiber and is produced from food grade high-amylose maize starch. Acid hydrolysis and heat treatment both reduce the digestibility of this high-amylose maize starch resulting in increased RS4 and total dietary fiber in the finished product. There are no nonstarch polysaccharides present in VERSAFIBE™ 2470. The nutrition composition of the Fiber Scone and Control Scone are shown in the following table.

 

Per Serving, As-Eaten

Control Scone

Fiber

Scone

Weight (g)

83.9

84.1

Calories (kcal)

328

270

Fat (g)

16.0

14.4

Saturated fat (g)

5.0

4.7

Protein (g)

7.1

6.1

Total Carbohydrates (g)

42.8

46.4

Available Carbohydrates (g)

38.8

28.9

Dietary Fiber (g)*

4.0

17.5

Sugars (g)

14.8

14.9

*VERSAFIBE™ 2470 resistant starch provided 16.5 g dietary fiber in the Fiber Scone

The subjects attended 3 study visits, one for screening and two test visits. At the test visits, subjects consumed the Control Scone or Fiber Scone (randomly assigned sequence) with 240 mL water.  Capillary glucose, plasma glucose and plasma insulin were measured pre-consumption and at t = -15, 15, 30, 45, 60, 90, 120 and 180 min ± 2 min, where t = 0 was the start of the study product consumption. Satiety visual analog scale (VAS) ratings were assessed pre-consumption and at 3 min intervals.  Questionnaires were used to assess Gastrointestinal (GI) Tolerability and product palatability at each test visit.

 Results:

A total of 36 subjects were randomized in the study, and one was withdrawn due to non-compliance. Ultimately, 32 subjects were included in the glucose and insulin analyses and 35 were included in the satiety VAS, GI tolerability and palatability analyses.

Consumption of the Fiber Scone significantly reduced postprandial glucose and insulin incremental areas under the curve (43-45% reduction and 35-40% reduction, respectively, p<0.05 for both) as well as postprandial glucose and insulin maximum concentrations (8-10% and 22% reductions, respectively, p<0.05 for both).  Ratings of hunger and desire to eat were also significantly reduced following consumption of the Fiber Scone vs. the Control Scone during the 180 minutes after intake (p<0.05) and there were no GI side effects with the Fiber Scone compared with Control.

Comment:

This study shows significant reductions in postprandial glucose and insulin levels associated with the replacement of refined carbohydrate with RS4 in healthy subjects. In addition, ratings of hunger and desire to eat were reduced after consumption of the RS4-containing food product, a first for this specific RS ingredient. Incorporation of a fiber such as RS4 into the diet has potential clinical and practical relevance due to favorable impacts on markers of cardiometabolic health.12,13

References:

  1. Stewart ML, Wilcox ML, Bell M, Buggia MA, Maki KC. Type-4 resistant starch in substitution for available carbohydrate reduces postprandial glycemic response and hunger in acute, randomized, double-blind, controlled study. Nutrients. 2018;10(2).
  2. Dahl WJ, Stewart ML. Position of the Academy of Nutrition and Dietetics: Health implications of dietary fiber. J Acad Nutr Diet. 2015;115:1861-1870.
  3. Stephen AM, Champ MM, Cloran SJ, et al. Dietary fibre in Europe: current state of knowledge on definitions, sources, recommendations, intakes and relationships to health. Nutr Res Rev. 2017;30:149-190.
  4. Tosh SM. Review of human studies investigating the post-prandial blood-glucose lowering ability of oat and barley food products. European J Clin Nutr. 2013;67:310-317.
  5. Robertson MD. Dietary-resistant starch and glucose metabolism. Curr Opin Clin Nutr Metab Care. 2012;15:362-367.
  6. Haub MD, Hubach KL, Al-Tamimi EK, Ornelas S, Seib PA. Different types of resistant starch elicit different glucose reponses in humans. J Nutr Metab. 2010;2010.
  7. Al-Tamimi EK, Seib PA, Snyder BS, Haub MD. Consumption of cross-linked resistant starch (RS4(XL)) on glucose and insulin responses in humans. J Nutr Metab. 2010;2010.
  8. Martinez I, Kim J, Duffy PR, Schlegel VL, Walter J. Resistant starches types 2 and 4 have differential effects on the composition of the fecal microbiota in human subjects. PLoS One. 2010;5:e15046.
  9. Shimotoyodome A, Suzuki J, Kameo Y, Hase T. Dietary supplementation with hydroxypropyl-distarch phosphate from waxy maize starch increases resting energy expenditure by lowering the postprandial glucose-dependent insulinotropic polypeptide response in human subjects. Br J Nutr. 2011;106:96-104.
  10. Gentile CL, Ward E, Holst JJ, et al. Resistant starch and protein intake enhances fat oxidation and feelings of fullness in lean and overweight/obese women. Nutr J. 2015;14:113.
  11. Stewart ML, Zimmer JP. Post-prandial glucose and insulin response to high-fiber muffin top containing resistant starch type 4 in healthy adults: a double-blind, randomized, controlled trial. Nutrition. 2018 (in press).
  12. Maki KC, Pelkman CL, Finocchiaro ET, et al. Resistant starch from high-amylose maize increases insulin sensitivity in overweight and obese men. J Nutr. 2012;142:717-723.
  13. Marlatt KL, White UA, Beyl RA, et al. Role of resistant starch on diabetes risk factors in people with prediabetes: design, conduct, and baseline reuslts of the STARCH trial. Contemp Clin Trials. 2018;65:99-108.
tape measure

Dr. Ralph Defronzo Interview

Dr. Ralph Defronzo Interview

Dr. Ralph Defronzo Interview

Dr. Ralph Defronzo Interview

Steve Freed, RPh, CDE from Diabetes in Control conducted a terrific interview with Ralph DeFronzo, MD, who is an endocrinologist and Deputy Director of the Texas Diabetes Institute.  Dr. DeFronzo has been a pioneer in conducting studies to elucidate the pathophysiology of type 2 diabetes mellitus, and in the evaluation of treatment strategies that address the underlying defects.  Dr. DeFronzo recently surpassed 750 publications and it is difficult to overstate his influence on the field of diabetology.  The full interview on video and a transcript may be obtained at www.diabetesincontrol.com and http://www.diabetesincontrol.com/dr-ralph-defronzo-full-transcript/.

Below is a summary of Dr. DeFronzo’s key points.

  1. Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) are two subtypes of prediabetes with different pathophysiologies:
    • IFG is characterized by hepatic insulin resistance and impaired first-phase insulin secretion;
    • IGT is characterized by skeletal muscle insulin resistance and impairment of second-phase insulin secretion.
  2. Progressive loss of pancreatic beta-cell function is the hallmark of progression from prediabetes to type 2 diabetes mellitus (T2D), and then to more severe T2D. Impairment of beta-cell response is due to a combination of dysfunction (hibernation) and loss of beta-cell mass.  This process can be arrested or slowed by drug therapies that have direct or indirect effects.
    • Direct effects – thiazolidinediones and GLP-1 agonists appear to have direct effects on the pancreas that help to preserve beta-cell mass, in part through reducing apoptosis.
    • Indirect effects – other drugs that lower glucose will reduce glucose toxicity, which, in turn, will improve beta-cell function and insulin sensitivity. DeFronzo believes that sulfonylureas should rarely be used and favors metformin and SGLT-2 inhibitors over other classes of glucose-lowering drugs.
  3. Recently published data support effects of three classes of hypoglycemic agents to reduce cardiovascular risk.
    • Pioglitazone (a thiazolidinedione) – the IRIS trial
    • SGLT-2 inhibitors – EMPA-REG Outcome and CANVAS
    • GLP-1 agonists – SUSTAIN-6 and LEADER
  4. DeFronzo advocates triple-therapy from early in the disease process (which can be costly) to address the underlying insulin resistance and arrest the progression of beta-cell impairment. This involves use of:
    • Pioglitazone (a thiazolidinedione),
    • A GLP-1 agonist,
    • Metformin or an SGLT-2 inhibitor.

Abbreviations:  CANVAS, Canagliflozin Cardiovascular Assessment Study; EMPA-REG, Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients; GLP-1, glucagon-like peptide-1; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; IRIS, Insulin Resistance Intervention after Stroke; LEADER, Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results; SGLT-2, sodium-glucose cotransporter-2; SUSTAIN-6, Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes; T2D, type 2 diabetes mellitus.

Relevant references

Abdul-Ghani M, Migahid O, Megahed A, Adams J, Triplitt C, DeFronzo RA, Zirie M, Jayyousi A. Combination therapy with exenatide plus pioglitazone versus basal/bolus insulin in patients with poorly controlled type 2 diabetes on sulfonylurea plus metformin: The QATAR Study. Diabetes Care. 2017;40:325-331. Erratum: 2017 June 14 [Epub ahead of print].

DeFronzo RA. Banting Lecture. From the triumvirate to the ominous octet: A new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009;58:773-795.

Kaul S. Mitigating cardiovascular risk in type 2 diabetes with antidiabetes drugs: A review of principal cardiovascular outcome results of EMPA-REG OUTCOME, LEADER, and SUSTAIN-6 trials. Diabetes Care. 2017;40:821-831.

Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, Shaw W, Law G, Desai M, Matthews DR, for the CANVAS Program Collaborative Group. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017 June 12 [Epub ahead of print].

 

Dr. Ralph Defronzo Interview