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Glycemic Research Laboratories


This report is the sole property of Glycemic Research Laboratories/Glycemic Solutions (GS) Corporation, and may not be copied in any format or portion without express prior written permission from GS. Official Document # 77124

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Table I


The American Diabetes Association (ADA)
American Association of Clinical Endocrinologists (AACE) 

Glycemic Research Laboratories

Glycemic Solutions Corporation

Clinical Testing Services



Glycemic Research Laboratories

Glycemic Solutions Corporation

Clinical Testing Services

Study Options

Glycemic Research Laboratories

Glycemic Solutions Corporation

Clinical Testing Services

Research Design and Methods

Glycemic Research Laboratories

Glycemic Solutions Corporation

Clinical Testing Services

Mathematic Modeling Methods In Glycemic Index Testing


  • In-Real-Time analytical testing methods

  • Standardized Board-Approved clinical protocols

  • Staff Physician’s Highly Trained in Glycemic Testing Protocols

  • Specific protocols for -0-, low-end, and high-end carbohydrate Test Foods

  • Product development trials 

  • Age, ethnic, and metabolic profile Targeted-Protocols

  • Diabetic, non-diabetic, insulin resistant testing protocols




The typical variable and error rate in global glycemic testing has been shown to reach 80 percent, which is not acceptable for United States (U.S.) government claims on foods. To reduce this error-rate and variable down to less than 2 percent, Glycemic Research Laboratories (GRL) re-structured and re-designed glycemic testing protocols, which are now utilized in every clinical study. 


Additionally, glycemic indices for foods can differ by fivefold, depending on level of adipose tissue body fat, metabolic Syndrome, BMI, insulin-resistance, diabetes, food form, and measurement/testing methods used. 

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Analysis Directive
Glycemic Research Laboratories
Copyright © 2007
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Simultaneous ingestion of carbohydrate and protein reduces glycemic response in some foods, while protein ingestion increases insulin response. Ingesting carbohydrates with fat typically blunts blood glucose effect, but does not effect insulin. 


Glycemic Research Laboratories (GRL) testing protocol has the highest rate of accuracy available (less than 2 % variability), with specific in-real-time analytical testing methods specifically developed by Glycemic Research Laboratories.


Specific protocols have been developed by Glycemic Research Laboratories for testing carbohydrate foods versus protein foods versus -0- calorie and low calorie foods.


Each GRL clinical protocol is designed to mitigate variables and stay within FDA and FTC legal guidelines for claims.


The variable reduction methodologies designed by Glycemic Research Laboratories are proprietary.




Targeted protocols are available to clients seeking clarification in glycemic and other metabolic responses. Targeted protocol subjects are selected on the basis of:


  • Age

  • Ethnicity

  • Genetic Polymorphisms related to obesity (leading in-house genetic specialist)

  • Somatotype

  • Insulin-disorders

  • Diabetics (type I and II)

  • Obese and BMI-differential


Analysis Directive
Glycemic Research Laboratories
Copyright © 2007
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High glycemic foods and beverages that elevate blood glucose and insulin levels cause weight gain, increased diabetes risk, and tremendous metabolic stress on the human body, as the body compensates for excessive insulin levels by producing more adrenaline, cortisol, and other stress hormones. 


Adrenaline, cortisol, and other stress hormones have two major effects:

1) They boost the blood levels of free fatty acids (FFA) and glucose. High

glucose levels trigger more insulin release, perpetuating the cycle.

2)The stress hormones act with high sugar levels and insulin itself to

raise the blood pressure, damage the sensitive endothelial cells that line

the arteries, and trigger the blood clots that can form on cholesterol-laden

plaques to produce heart attacks and strokes.

High glycemic meals promote elevated blood glucose and insulin levels, as well as direct adipose tissue fat storage. The glucose excursion that follows a low versus a high glycemic index meal directly affects postprandial glycemia. As an example, the change in plasma glucose one hour after eating 50 g of spaghetti is half of that seen 1 hour after eating 50 g of white bread (Reference: Glycemic Research Laboratories clinical trial for Mueller’s Pasta).



High glycemic meals > Postprandial hyperglycemia >

Increased circulating free fatty acids > 

Independently contribute to glucotoxicity >

Oxidative stress > lipotoxicity > insulin resistance > hyperinsulinemia


The glycemic response to a mixed meal can be identified by feeding subjects weighed portions of a mixed meal with varying percentages of carbohydrates, proteins, and fat.

Glycemic Research Laboratories conducts trials on mixed meals and frozen meals.


Analysis Directive
Glycemic Research Laboratories
Copyright © 2007
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• Calorie for calorie, high glycemic foods produce higher insulin levels

than low glycemic foods.

Foods and beverages with -0- calories and -0- carbohydrates can

elicit high insulin levels


The Glycemic Response of foods & beverages refers to the effects elicited by oral ingestion of any edible agent (not just carbohydrate foods) on blood glucose concentration and insulin levels during the digestion process.

All foods and beverages can be designed and/or re-formulated to moderate and reduce blood glucose and insulin responses by utilizing Glycemic Research Laboratories Clinical Investigation Protocols.

The Nurses’ Health Study, Harvard Medical School, found that “Women who ate the most foods with a high glycemic index had a 50% greater risk of diabetes than those who ate the least.” 


The study went on report: “Not all foods affect blood glucose levels in the same way. Some foods have what is called a high glycemic index, which means that they can raise blood glucose levels rapidly. 


Eating a lot of high glycemic index foods forces the body to produce insulin in large amounts to try to clear the high levels of glucose in the blood. Over time, this increase in insulin production can increase the risk of diabetes.”


Glycemic Research Laboratories Clinical Investigation Protocols provide a better understanding of the diabetic properties and risk associated with foods and beverages, as well as Nutraceuticals and Pharmaceuticals. 


This allows for proper formulation and marketing of said products, and for design and re-formulating options by clients.


Volume 9, 2003
Nurses’ Health Study 
Harvard Medical School


Analysis Directive
Glycemic Research Laboratories
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The American Diabetes Association (ADA) and the American Association of Clinical Endocrinologists (AACE) recommend specific target goals in achieving blood glucose control 
(Table I).









Analysis Directive
Glycemic Research Laboratories
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In the development of sports-performance-related-products, professional athletes may be utilized. High glycemic sports drinks reduce sports performance (GRI Human Maximum Performance report), and are therefore contraindicated for professional athletes.


Zero-calorie beverages are no longer the answer to the growing obesity issue. Beverages that contain -0- calories and -0- carbohydrates are capable of increasing diabetes risk, and adding body weight, via the Cephalic Response. 


Therefore, typical glycemic studies are no longer the sole answer to understanding the metabolic response of beverages. 


Services are available to beverage clients seeking to identify the biochemical properties of a beverage, or to re-design current beverage products, and/or to develop new beverages. Targeted Clinical Investigation Protocols seek to identify the major factors involved in creating beverages. 


Beverages focusing on the “Diet” market are encouraged to select protocols targeted to analyze:

•Glycemic response

•Diabetic response

•Adipose tissue fat-storing response

•Cephalic response

Sugars and sweeteners, despite the caloric or carbohydrate content, are capable of high glycemic reactions on blood glucose and insulin levels. Sweeteners previously believed to have a glycemic response of zero have recently been proven to have definite glycemic properties. 


In the case of sweeteners, the Test Food is prepared per instructions and confirmed by Brix refractometry.


Doses as low as 1 gram of Stevia elicit a glycemic index in clinical trials. As doses of Stevia increase, so does the glycemic index. 

Analysis Directive
Glycemic Research Laboratories
Copyright © 2007
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Sugar alcohols, or polyols, are hydrogenated carbohydrates that are used in foods primarily as sweeteners and bulking agents. Sugar alcohols possess varying glycemic responses, and are not inert, as they exert glycemic responses, as well as increasing FFA. Free fatty acids (FFA) and 3-hydroxybutyric acid levels increase after erythritol (sugar alcohol) administration.


Sugar alcohols are not the preferred sweetener or bulk, as they can cause flatulence or a laxative effect in varying degrees in some individuals. This is due to their incomplete absorption (in the small intestine) properties.


Many food manufacturers claim that sugar alcohols do not affect blood sugar levels, but in reality, they do affect the postprandial blood glucose response in individuals both with and without diabetes.




Glycemic Research Laboratories has designed two separate Protocols for glycemic clinical

testing based on the carbohydrate content of the test food:


•Protocol I is designed for carbohydrate-rich foods

Carbohydrate-rich foods are tested using 50 gram of carbs from the test food


Protocol II is designed for low carbohydrate and/or low-nutrient value foods

Very low-carb foods are tested using one-or-more servings as the test size

Proteins eaten without carbohydrates can induce high glycemic responses and fat storage in humans. Consumption of high amounts of meats or protein (more than 30 grams ingested at one time) triggers adipose tissue fat storage and spillage into the urea cycle, causing liver and kidney problems, such as elevated liver enzymes, which can disqualify individuals from obtaining personal health insurance. 


In many cases, ketogenic diets; high protein diets (Atkins, etc.), are responsible for skewed blood profiles. 


Removing the patient from a high protein diet for 4-6 weeks typically returns serum profiles to normal.


Analysis Directive
Glycemic Research Laboratories
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Most alcoholic beverages contain low amounts of carbohydrate, ranging from 0 to 4 grams per 100 ml. Beer contains 3-4 grams of carbohydrate per 100 ml. Therefore, consuming large quantities of beer can over-elevate blood glucose levels. Consuming one glass of beer slightly elevates blood glucose levels.


The high caloric-values of alcohol respond to stimulation of fat-storage in humans. Favored-wines commonly contain high glycemic sugars, which can over-elevate blood glucose and insulin levels, independent of their alcohol content.


Legal use of the term “Low Glycemic” in the United States, as dictated by the Federal government, requires “appropriate serving size” amounts used in clinical tests. 


Appropriate serving sizes are utilized during GRL clinical studies. In order to make the claim of “Low Glycemic” for any human-grade food product, the United States government requires Board Approved human In Vivo clinical trials. 


In Vitro and non-clinical trial calculations, and/or software that claims to be able to determine glycemic index are not legally permitted for product labeling.




Glycemic Research Laboratories In Vivo Clinical trials focus on glycemic index, glycemic load, glycemic response, insulin response, Genetic Profiling, Metabolic Syndrome, fat-storing mechanisms and factors; Lipoprotein Lipase, Leptin, Neuropeptide Y, and Cephalic Response.


Test Food (s) are fed to pre-screened human subjects selected for specific protocols, such as diabetics, non-diabetics, obese, age, ethnic, children, and targeted other groups. 


Protocols are designed by the GRL Medical Advisory Board (see About Us at www.GlycemicResearchLaboratories.combased on the Protocol Design Session.



The client participates in a Protocol Design Session prior to the testing phase, which includes:

• Targeted subject group for trials

• Age group

• Adipose Tissue Fat Shunting Proclivities

• Genetic Variances in Obesity (see below)

• Metabolic Syndrome (see below) 

• Duration of trial

• Number of subjects in trial (Pool Size)

• Cross-Analysis trials (comparative)

• Percent glycemic reduction in comparative trials

• Beverage analysis (liquid with/without nutrient value)

• -0- Calorie protocols

• Palatability: taste and mouth-feel profiles (per subject opinions)

• Journal publication options 


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Glycemic Research Laboratories
Clinical Testing Methodologies
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According to the American Diabetes Association (publication January 2007), “Half the U.S. population has the gene that puts them at greater risk of developing diabetes. The gene causes people to metabolize fat differently and may hurt their ability to remove sugar from the blood.” This genetic variant alters the way half the population in America processes food, driving foods into fat cells.


Many other genetic traits in humans have been identified which alter food and beverage metabolism. Foods and beverages can be formulated to address genetically-hard-wired metabolic variances as related to obesity, overweight, fat-cell activity, diabetes, and insulin-disorders.

In Diabetes Today
26-JAN-2007; Half the Country Has Diabetes Gene

Clients may elect to utilize subjects with Metabolic Syndrome as defined herein, or to eliminate all subjects diagnosed in-house with Metabolic Syndrome.


1.Abdominal obesity (waist circumference 40 inches or more)**

2.Fasting triglyceride levels of 150 mg/dL or higher

3.HDL cholesterol levels below 40 mg/dL**

4.Blood pressure of 130/85 mm Hg or higher

5. Fasting blood sugar of 110 mg/dL or higher


*per Harvard University Health Publications 2006

**35-inch waist for women

***HDL below 50 for women













Clients submitting new products may opt for New Product Trial Feedback (NPTF) prior to finalizing a formula. 


This option entails pre-testing of formulas to develop the most glycemically acceptable form of the Test Food, assistance with ingredients selection, pre-screening and testing of formula ingredients and options, and preferred-outcome selection of formula raw materials.


Glycemic Research Laboratories, Medical Advisory Board, represent expertise in glycemic product development, having received the first glycemic patent ever awarded worldwide. For the past 23 years, GRL staff has been at the forefront of glycemic research and development.


Glycemic Research Laboratories is bound to protect, and hold private, trade and formula secrets involved in product testing and product development. GRL does not publish any clinical trial results, without express written permission from clients, as this would compromise proprietary product development.


GRL proprietary low glycemic, non-Cephalic development protocols are held in strict confidence by the GRL development staff, and are not made public in any circumstances whatsoever.


In the case of proprietary product development, and patent applications, Glycemic Research Laboratories will not accept competing-development projects (on a case-by-case basis). 


Glycemic Research Laboratories conducts testing and product development for the largest food companies in the world, and as such, does not compromise proprietary trade secrets.

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Glycemic Research Laboratories
Study Options
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If clients intend to apply for the Glycemic Research Institute (GRI) Certification Marks; Low Glycemic and/or Low Glycemic for Diabetics, GRL will apply appropriate protocols during the trial period, as specified by GRI’s guidelines. 


To utilize GRI’s Diabetic Certification Marks, it is mandatory to use diabetic subjects, as diabetics respond very differently than non-diabetics to foods, drinks, and Nutraceuticals ingested. 


The Glycemic Research Institute is a non-profit organization that allows Pro Bono use of its Federally registered Certification Marks, based on submitted and accepted Human In Vivo Clinical trials. The Glycemic Research Institute does not accept In Vitro or non-approved clinical trials as acceptable proof of glycemic response. The certification Marks may be viewed at


Protocols can be specifically designed to meet the requirements of peer reviewed journals. This must be implemented prior to the onset of the GRL clinical trial.














The glycemic index is a numerical classification based on Human In Vivo clinical trials designed to quantify the relative blood glucose response to foods, drinks, Nutraceuticals, Pharmaceuticals, and any edible agent. 


Glycemic Research Laboratories (GRL) Human In Vivo Clinical trials have been developed over a 20-year period, focusing on reduction of testing variables. GRL trials are conducted under direction of the Glycemic Research Laboratories (GRL) Medical Advisory Board, M.D.’s, Professor’s of Medicine, and PhD statisticians.

Medical Advisory Board: See About Us at:

Testing methods are approved by the Institutional Review Boards for the State of Florida, and the International Clinical Study Review Board. Specific analytical testing methods are the property of GRL.


All blood work and analytical calculations are conducted in-house in Real-Time. Utilizing standardized Glycemic Research Laboratories Board-Approved clinical protocols, accommodations are made for low-end or high-end carbohydrate Test Foods. 


Ten pre-screened human subjects are typically used for each product tested. Clients may elect to use larger pools of subjects.


White bread is used as the standard. Each subject is fed a minimum of three bread standards for comparison to the products tested. Calculations are made using the area under the curve (AUC) as compared to bread standards (converted to the glucose scale). AUC is calculated by GRL statisticians using standard Glycemic Research Laboratories protocols.


Fasting blood glucose measurements are made, and at 15-minute intervals throughout the trial, for 2-4 hours, or until blood glucose levels stabilize.

Capillary blood is preferred: the results for capillary blood glucose (BG) are less variable than that of venous plasma glucose. Additionally, elevations in BG are greater in capillary blood than venous plasma, and the differences in Test Foods and bread standards are easier to detect statistically using capillary blood glucose. 

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Glycemic Research Laboratories
Research Design & Methods
Copyright © 2007
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When VBP is called for in clinical trials, the GRL protocol calls for an overnight fast of 12 h, a blood sampling i.v. cannula was inserted into the antecubital vein. Blood samples are taken at -5, -10 and -15 minutes (analysed as a pool) before the Test Food, and every 15 minutes for the first hour, and every 30 minutes thereafter, to a 5-hour postprandial period. 

Taste, mouth-feel, gastrointestinal issues; nausea, flatulence, bloating, are recorded.

Results presented in the final Test Food report are based on the glucose scale. Glycemic index and glycemic load values are converted to the glucose = 100 scale by multiplication with the factor 0.7. 

SUBJECTS undergo a two-visit protocol, the first to determine glucose tolerance status and the second to measure SI. Subjects fast for 12 h before each of the two visits, and abstain from alcohol for 24 h. Smoking is prohibited on the day of the study.

Anthropometric measures are taken for each subject. Height and weight are measured in duplicate and recorded to the nearest 0.5 cm and 0.1 kg, respectively. BMI is calculated as weight (in kilograms) divided by the square of height (in meters). Waist circumference is measured at the natural indentation or at a level midway between the iliac crest and the lower edge of the rib cage if no natural indentation was visible. Waist is recorded to the nearest 0.5 cm, and the mean of two measures within 1 cm of each other is used. 

• Waist circumference (cm)

• Disposition index

• BMI (kg/m2)

• Insulin sensitivity (min–1 • µU–1 • mL–1 • 10–4)

• Fasting insulin (pmol/l)

• AIR (µU • ml–1 • min–1)

A 2-h, 75-g oral glucose tolerance test is performed during the first visit, and World Health Organization (WHO) criteria is used to assign glucose tolerance status. Subjects taking oral hypoglycemic medications are classified as type 2 diabetics.


Glycemic Research Laboratories
Research Design & Methods
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Acute insulin response (AIR) and SI are assessed using a 12-sample, insulin-enhanced, frequently sampled intravenous glucose tolerance test (FSIGT) with minimal model analysis. Modifications of the protocol are used when appropriate for targeted Trials. AIR and fasting insulin are log transformed: logarithmic transformations, the disposition index, typically calculated as the product of AIR and SI, is preferentially created as the sum of log (AIR + 20) and log (SI + 1). 

AIR is calculated based on insulin levels through the 8-min blood samples before insulin infusion. Fasting plasma insulin was determined by radioimmunoassay.

SI is calculated by mathematical modeling methods; the time course of plasma glucose was fit using nonlinear least squares methods with the plasma insulin values as a known input to the system. 

Mean glycemic index values are assigned to white bread standard purchased at available grocery stores.

In our subject pre-screening, typical glycemic index (GI) and glycemic load (GL) are 58 and 128 g/day, respectively. A higher SI value expresses increased insulin sensitivity, while higher fasting insulin implies increased insulin resistance. Higher AIR indicates greater insulin secretion in response to glucose, and higher disposition index implies increasing pancreatic functionality. Positive linear relationships are observed between food/liquid intake and levels of fasting insulin, BMI, and waist circumference.

Adjustments are made for non-carbohydrate Test Foods using the Residual Method.

Dietary fiber intake and measures of SI, insulin secretion and adiposity are made, including multivariate adjustment and scoring, as dietary fiber in a Test Food is associated with SI, fasting insulin, BMI, and waist circumference. In our trials, it is observed that 1 8-10 gram fiber content is associated with lower level of fasting insulin with statistically higher level of SI. Significant linear relationship between glycemic load and outcome levels is observed, that are positive for fasting insulin, BMI, and waist circumference and inverse for SI. 

Outliers are recorded.


Subject responses to Test Food activation of adipose-tissue fat-storage mechanisms, IE LPL, are tracked and recorded per GRL protocols.


Glycemic Research Laboratories
Research Design & Methods
Copyright © 2007
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If Cephalic Response testing is included in the protocol, it is recorded during the first 60 seconds after the subjects have mouth-contact with the Test Food, and for 30-second intervals thereafter. Swallow versus non-swallow protocols are utilized for accuracy, as digestion of dietary carbohydrates starts in the mouth, where salivary a-amylase initiates starch degradation. 

Venous blood samples for insulin and FFA are collected in glass tubes and allowed to coagulate on ice for 10 min, then stored immediately at -20°C until analysis (IN-REAL-TIME).

Blood glucagon samples are taken in Vacutainer-EDTA with Trasylol® added (50µl/ml of blood), and then plasma is obtained and processed immediately. 

Serum glucose is assayed by the glucose oxidase method (Photometric Instrument 4010, Roche, Basel, Switzerland).

GI (%) = ∑(carbohydrate content of each food item (g) × GI)/total amount of carbohydrate in meal (g); GL (g) = ∑(carbohydrate content of each food item (g) × GI)/100. 

Area beneath baseline is not utilized.

Serum glucose and insulin postprandial responses are assessed using incremental (iAUC) and total area under the curve (tAUC) at 2 h, 5 h and between 2–5 h. Serum FFA and plasma glucagon postprandial responses are assessed using the tAUC at 2 h, 5 h and between 2–5 h. iAUC and tAUC are geometrically calculated using the trapezoidal method. 

The glycemic index (GI) of a particular food is determined by calculating the incremental area under the blood glucose response curves (iAUC) for that food compared with a standard control of white bread (utilizing the trapezoid rule).

Glycemic Response and Cephalic Response are defined differently, are based on ingestion of Test Foods and beverages that have nutrient value, and -0- nutrient value.

Refers to the effects elicited by oral ingestion of any edible agent (not just carbohydrate foods) on blood glucose concentration and insulin levels during the digestion process.


Glycemic Research Laboratories
Research Design & Methods
Copyright © 2007
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Glycemic Index (GI) alone is unable to predict the glycemic response/impact when different amounts of carbohydrates are eaten. Glycemic Load must be utilized in conjunction with GI to differentiate the acute impact on blood glucose and insulin responses induced by Test Foods.

Glycemic Load is based on a specific quantity and carbohydrate content of the test food. GL is calculated by multiplying the weighted mean of the dietary glycemic index by the percentage of total energy from the test food.


When the test food contains quantifiable carbohydrates, the Glycemic Load equals GI (%) x grams of carbohydrate per serving. One unit of GL approximates the glycemic effect of 1 gram of glucose. Typical diets contain from 60-180 GL units per day.

A HIGH GLYCEMIC LOAD diet is defined as: 60% carbohydrate, 20% protein, 20% fat (glycemic load 116 g/1000 kcal).

A LOW GLYCMIC LOAD diet is defined as: 40% carbohydrate, 30% protein, 30% fat, (glycemic load 45 g/1000 kcal). 

Results presented in the final Test Food report are based on the glucose scale. Glycemic index and glycemic load values are converted to the glucose = 100 scale by multiplication with the factor 0.7. 


The following Human In-Vivo Clinical Trial was conducted by Glycemic Research Laboratories (GRL) in 2007, and is utilized as an example (Report ID: GTD-0307) of a typical GRL clinical trial. No copies of this report may be made, transferred, or used in any format whatsoever, and remains the sole property of Glycemic Research Laboratories.

















The following references represent Glycemic Research Laboratories review and adoption of protocols and methods utilized in Glycemic Index Testing.

These include mathematical models used in the clinical identification of specific aspects of blood glucose, insulin, diabetes, insulin resistance, and other related metabolic perimeters. Various deterministic and stochastic tools are available, both simple and comprehensive, in evaluating trial data, which include partial differential equations, integral equations, matrix analysis, optimal control theory, differential equations, and computer algorithms.

Mari A. Mathematical modelling in glucose metabolism and insulin secretion. Current Opinion Clinical Nutrition Metabolism Care. 2002;5:495–501. doi: 10.1097/00075197-200209000-00007

Boutayeb A, Twizell EH, Achouyab K, Chetouani A. A mathematical model for the burden of diabetes and its complications. Biomedical Engineering Online. 2004;3:20. doi: 10.1186/1475-925X-3-20.

Boutayeb A, Chetouani A, Achouyab K, Twizell EH. A non-linear population model of diabetes mellitus. Journal of Applied Mathematics and Computing. 2006;21:127–139. 

T. J. Orchard et al. Modeling Chronic Glycemic Exposure Variables as Correlates and Predictors of Microvascular Complications of Diabetes: Response to Dyck et al; Diabetes Care, February 1, 2007; 30(2): 448 - 448.

Bergman RN, Finegood DT, Ader M. Assessment of Insulin Sensitivity in Vivo. Endocrine Reviews. 1985;6:45–86

Bergman, RN. The minimal model of glucose regulation: a biography. In: Novotny, Green, Boston., editor. Mathematical Modeling in Nutrition and Health. Kluwer Academic/Plenum; 2001

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Mathematic Modeling Methods
Glycemic Research Laboratories.
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Bergman, RN. The minimal model: yesterday, today and tomorrow. In: Bergman RN, Lovejoy JC., editor. The minimal model Approach and Determination of Glucose Tolerance. Vol. 7. Boston: Louisiana State University Press; 1997. pp. 3–50

Nucci G, Cobelli C. Models of subcatuneous insulin kinetics: a critical review. Computer Methods and Programs in Biomedicine. 2000;62:249–257. doi: 10.1016/S0169-2607(00)00071-7

Bellazzi R et al. The Subcutaneous Route to Insulin Dependent Diabetes Therapy: Closed-Loop and Partially Closed-Loop Control Strategies for insulin Delivery and Measuring Glucose Concentration. IEEE Engrg Medicine Biol. 2001;20:54–64. doi: 10.1109/51.897828

The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus: Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 20:1183–1197, 1997

Makroglou A, Li J, Kuang Y. Mathematical models and software tools for the glucose-insulin regulatory system and diabetes: an overview. Applied Numerical Mathematics. 2006;56:559–573. doi: 10.1016/j.apnum.2005.04.023. 

Parker RS et al. The Intraveneous Route to Blood Glucose Control: A Review of Control Algorithms for Noninvasive Monitoring and Regulation in Type 1 Diabetic Patients. IEEE Engineering in Medicine and Biology.. 2001;20:65–73. doi: 10.1109/51.897829. 

Koschinsky T, Heinemann . Sensors for glucose monitoring: technical and clinical aspects. Diabetes/Metabolism Research and Reviews. 2001;17:113–123. doi: 10.1002/dmrr.188. 

Della C, Romano MR, Voehhelin MR, Seriam E. On a mathematical model for the analysis of the glucose tolerance curve. Diabetes. 1970;19:145–148. 

Bolie VW. Coefficients of normal blood glucose regulation. J Appl Physiol. 1961;16:783–788.] 

Serge G, Turcogl M, Varcellone G. Modelling blood glucose and insulin kinetics in normal diabetic and obese subjects. Diabetes. 1973;22:94–97. 

Mukhopadhyay A, De Gaetano A, Arino O. Modelling the intra-venous glucose tolerance test: A global study for single-distributed-delay model. Discrete and Continuous Dynamical Systems Series B. 2004;4:407–417. 


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Mathematic Modeling Methods
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Ackerman E, Gatewood LC, Rosevear JW, Molnar GD. Model studies of blood glucose regulation. Bull Math Biophys. 1965;27:21–24. 

Srinivasan R, Kadish AH, Sridhar R. A mathematical model for the control mechanism of free-fatty acid and glucose metabolism in normal humans. Comp Biomed Res. 1970;3:146–149. doi: 10.1016/0010-4809(70)90021-2. 

Brownlee M: Biochemistry and molecular cell biology of diabetic complications. Nature 414:813–820, 2001

Bergman RN, Ider YZ, Bowden CR, Cobelli C. Quantitative Estimation of Insulin Sensitivity. Am J Physiol. 1979;23:E667–E677. 

Cobelli C, Mari A. Validation of mathematical models complex endocrine-metabolism systems. A case study on a model of glucose regulation. Med & Biot Eng & Comput.1983;21:390–399. 

Orchard TJ, Forrest KY, Ellis D, Becker DJ: Cumulative glycemic exposure and microvascular complications in insulin-dependent diabetes mellitus: the glycemic threshold revisited. Arch Intern Med 157:1851–1856, 1997

DCCT Research Group: The Diabetes Control and Complications Trial (DCCT): design and methodologic considerations for the feasibility phase. Diabetes 35:530–545, 1986