Presentation Objectives Diabetes statistics

Presentation Objectives

• Diabetes statistics

• What is chromium?

• What is biotin?

• What is Diachrome®?

• Discuss the role of chromium (Cr+3) and biotin in insulin and carbohydrate metabolism.

• Discuss the results of Diachrome® T2DM clinical trials.

• Economic considerations of Chromium

Cases of Diagnosed Diabetes in the U.S. by Age

Relationship Between Glycemia and Complications

Aggressive Control of Type 2 Diabetes is Critical

• American Diabetes Association

• Normal Goal

• A1C (%) <6 <7

• Preprandial plasma glucose (mg/dL) <110 90-130

• American Association of Clinical Endocrinologists

• A1C (%) <6 6.5

• Preprandial plasma glucose (mg/dL) <110 <110

Traditional Treatment Approach Adds Medications Sequentially

Nutritional Goals

• Individualized meal planning

• Balance food intake with medications and exercise

• Maintain reasonable weight

What about Chromium?

• Chromium is an essential cofactor for the hormone insulin which regulates the metabolism of protein, fat and carbohydrates.
• Chromium is a trace element found in brewers yeast, broccoli, organ meats, whole grains, cheese and nuts.

Chromium and Diet

• Inadequate amount of chromium in the US diets

• foods containing chromium not frequently eaten
• chromium is lost during food processing

• Diets rich in sugar and carbohydrates cause a loss of chromium

• lower Cr levels than normal in obese and/or diabetes

• Chromium levels with age

Complex of chromium (Cr+3) and picolinic acid

• Complex of chromium (Cr+3) and picolinic acid

• Cr is an essential trace mineral

• Picolinic acid is a natural metabolite of tryptophan

• Found in higher levels in human breast milk

• Picolinic acid enhances the absorption/bioavailability of Cr

What is biotin?

• Biotin; a water soluble B vitamin

• (C10H16N2O3S) ; MW = 224.31

• Stimulates activity of glucokinase

• Improves pancreatic β-islet cell function

• Regulates conversion of glucose to FA

Chromium Picolinate Safety

• Genotoxicity Studies (5)

• Sub-chronic (90 day) Mice/Rats (NTP)

• Sub-chronic (20 wk) Rat Toxicity (Anderson, 1997)

• Human Genotoxicity Study (Kato, 1998)

• 5 Isolated Case Reports - Never Duplicated

• No adverse effects seen in 30+ clinical studies

• Generally Recognized As Safe affirmed (2000)

• Institute of Medicine 2004 Review Supports Safety

• UK FSA (2004): CrPic Safe For Use Up To 10 mg/d

• FDA QHC (2005): Finds CrPic Safe For Intended Use

Biotin - Safety

• No toxic effects reported

• No AEs with 200 mg orally

• No LOAEL (Lowest Observed Adverse Event Level)

• NOAEL = 2500 mcg (2.5 mg)

• GRAS (Generally Recognized as Safe)

What is Diachrome®?

• An adjuvant comprised of:

• Chromium Picolinate (600 mcg Cr+3)
• Biotin (2 mg)

• Dual benefits include reduction of elevated blood glucose and improvement in blood lipids

• Once a day administration

Cr Levels Over Time (Progression of Diabetes)

Chromium in Tissues

Clinical Studies in Subjects with Diabetes (Effect on Blood Glucose Control)

Change in Fasting Insulin with CrPic

Mean Urinary Chromium Losses Following Corticosteroid Treatment (n=13)

CrPic Treatment of Steroid-Induced Diabetes

• 49 of 52 pts. reacted satisfactorily

• Fasting blood glucose levels decreased from 250 mg/dl to 150 mg/dl

• 5 pts. stopped taking hypoglycemic agents (sulfonylureas or insulin injections) and did well on Cr supplementation alone.

Diachrome® Studies

• In Vitro

• Human Skeletal Muscle Cells

• Preclinical

• JCR La:cp Rat Model

• Clinical

• PEP (Open Label Program) N=40
• Beverage (DBPC Study) N=34
• Glycemic Index (DBPC Study) N=43
• T2DM 90 day (DBPC Study) N=447
• T2DM 270 Day Extension N=28

CP+Biotin: Skeletal Muscle Cell Culture (Glucose Uptake & Glycogen Production)

Animal Study (JCR Rats) Glucose Metabolism & HDL Cholesterol

Diachrome® PEP Program *

• Open-label program in patients with type 2 diabetes

• Program showed improvements in blood sugar control

Diachrome® : PEP Results (12 week change in HbA1c levels, 40 subjects)

Diachrome® 30-Day Clinical Study Glycemic Index

Nutrition 21 CPB-02003 Diachrome® 90 Day Type 2 DM

• Randomized, Double Blinded, Placebo Controlled

• Multi-geographical Study Centers; N= 17

• Inclusion Criteria:

• Male or Female; 18-70
• BMI > 25 and < 35
• HbA1c > 7.0%
• Stable OADs > 60 days

• Total Enrolled: 447

• Cauc. 221; Hisp. 147; Blk. 48; Asian 23; Other 8
• Male 258; Female 189

• Intent To Treat: 369

• At least one dose of study med
• One A1c assessment post Baseline Visit

Diachrome® Study Results Effect on HbA1c Levels

Diachrome® Study Results Effect on TG/HDL Ratio

Diachrome® Study Results Effect on Total Cholesterol and LDL Cholesterol

Diachrome® Study Results Subjects with Baseline A1c > 10.0

Diachrome® Study Extension Phase

• 270 Day Extension Phase to 90 Day Study

• All subjects on active intervention

• Visits at 2, 4, 6, and 9 months post enrollment

• 28 subjects enrolled; 24 completed.

• OADs held steady

• No daily insulin use

Economic Analysis Model

• Statistical analysis used to estimate a range of potential 3-year cost savings

• Lifetime cost savings estimated by adjusting literature benchmark, and using price index to adjust for inflation

Literature Review of Economic Impact

• Gilmer showed that medical care charges increase for every one percentage point increase in HbA1C above 7 percent. The savings vary depending on level of HbA1C and other “diseases” that the patient may have

• Gilmer estimated that decrease in HbA1C would result in direct cost savings over a three year period:

• Only diabetes $ 805
• Diabetes & Hypertension $1,130
• Diabetes & Heart Disease $2,078
• Diabetes, Heart & Hypertension $2,675

Literature Review of Economic Impact

• Menzin, in a retrospective study, examined the potential short-term economic benefits of improved glycemic control:

• Change in Glycemic Control Cost Reduction

• (initial HbA1C to final HbA1C) (3-years)

• Fair to good
• (8%-10%) to (less than 8%) $ 410
• Poor to fair
• (10%+) to (8-10%) $1,660
• Poor to good
• (10%+) to (less than 8%) $2,070

Economic Analysis: 3-Year Savings Population-wide

Economic Analysis: Lifetime Cost Savings, Newly Diagnosed

• Approx. 1.3 million people diagnosed each year with diabetes; 90% with type 2

• Using Ginsberg’s estimated lifetime cost savings of $27,000 ($36,000 in 2004 dollars) per patient with good diabetes control, lifetime cost savings of those diagnosed with T2DM in 2004 calculates to approximately $42 billion

Perhaps we should finally start to look at nutrient based solutions as an approach to diabetes!