A Message from our Medical Director
Thank you for your interest in Trina Health West Los Angeles. We are delighted to introduce our new Diabetes treatment center and appreciate your time in learning more about us. According to the CDC, approximately 29 million Americans have been diagnosed with Diabetes. People with diabetes are at increased risk of serious health complications including retinopathy, nephropathy, heart disease, stroke, peripheral neuropathy, diabetic ulcers with amputations and premature death.
Trina Health West Los Angeles provides pulsatile insulin infusion treatment, which promotes the normalization of carbohydrate metabolism in diabetic patients. The process involves the administration of insulin pulses similar to those found in the portal circulation of non-diabetics using the Bionica Microdose® infusion device which is FDA cleared for this treatment. The process is monitored by glucose levels and metabolic measurements. Metabolic measurements are taken by a metabolic cart which determines the ratio of VCO2/ VO2. This ratio is specific for the fuel used at any one time by the body. Our goal is to provide significant improvement in diabetic symptoms and organ complications.
We look forward to working with you to help improve the lives of patients with Diabetes. Please find enclosed a brief overview of our clinic, supportive studies, and locations worldwide. We welcome you and your staff to come visit our office and tour the facility.
Rahul Dixit, MD
Medical Director, Trina Health of West Los Angeles
Introduction to Artificial Pancreas Treatment® (APT)
Treating diabetes – a reversible metabolic dysfunction.
Artificial Pancreas Treatment® using the Bionica Artificial Pancreas System® is the only US FDA cleared safe and effective way to stop the progression of diabetes and in most ways reverse the chronic complications of diabetes. It is uniformly effective for both Type 1 and Type 2 diabetic patients. APT has been shown to be effective in even the most impaired patients. It has been steadily developing with confirming published clinical trials for 24 years (See Publications).
Correcting the Core Problem: All scientists agree, diabetes is not a disease of improper blood sugars, they are the product of improper carbohydrate metabolism. Yet treatments have focused on blood sugar as a surrogate of this disease. The Artificial Pancreas Treatment® addresses this core problem by mimicking the natural way that a pancreas signals a liver to cause the upregulation of the Krebs Cycle, and restore carbohydrate metabolism.
Technical Deficiency: Diabetes is technically a lack of carbohydrate processing enzymes made by the liver. This results from insufficient stimulation of the liver by the pancreas. Fortunately, when the body metabolizes carbohydrates it stops converting high levels of lipids and free fatty acids, which directly cause all measurable complications of diabetes through metabolic inflammation, that is, improper levels of inflammatory cytokines (IL-6, IL-2, TNFα, NFkβ). Both free fatty acids and these cytokines are elevated when the diabetic patient cannot process carbohydrates properly.
The Missing Signal by the Pancreas: The first important role of insulin is to signal the liver to produce sufficient levels of the Kreb’s Cycle enzymes that are necessary for proper carbohydrate metabolism. APT uniquely addresses and restores proper enzyme levels as shown by metabolic measurement, and thus treats the core problem. Mimicking the natural stimulation of a pancreas using a sophisticated two-signal delivery process of intravenous insulin bursts and tailored glucose. APT has effectively restored proper metabolism in both type 1 and type 2 diabetes.
Result of Restoring the Kreb’s Cycle: With proper carbohydrate metabolism, two things occur. First, normal levels of cellular energy are restored (a diabetic person has approximately 70% of the intra- cellular energy of a non-diabetic person). And secondly, the destructive high lipid metabolism with elevated free fatty acids are reduced. Because lipid metabolism is the “back-up” system of providing nutrients to the cells, it was never meant to be the primary source of energy as it is with diabetes (T1DM and T2DM). Constant high lipid utilization automatically results in elevated lipids and free fatty acids, casing the entire diabetic milieu.
The Overview of Diabetes Complications: Clemens and colleagues published the following overview of diabetes and its “poor outcomes” which sets forth the causational relationship of improper carbohydrate metabolism and disability/death. It also shows the origins of all complications, the inability to properly process and metabolize glucose within the cells. Conventional therapies are not able to reestablish proper metabolism of carbohydrates by the mitochondria in the cell, and thus with any excess glucose, the patient has increased blood glucose.
The complexity of metabolism has caused many scientists to take a more focused (less organic) approach to chemically inducing changes. However, the quintessential approach to normalization is obtained by replicating normal pancreatic stimulation of the liver.
Current Pharma Approaches: All seek a glucose end-point, when glucose is a symptom.
The Great Misconception: It is well known and proven that intensive blood sugar control does NOT stop the complications of diabetes. However over-focus on glycemia causes this myth to still be prevalent, even though the DCCT, UKPDS, Ohkubo, and ACCORD Studies are consistent:
DCCT: “while not controlling glucose worsens complications, tight control does not prevent 25% to 40% of diabetic patients from developing overt secondary complications within 10 years.” Ohkubo: Near perfect blood glucose of HbA1c of < 6.5 and fasting blood glucose of < 110….. Still only reduced severity of complications and did not stop complications.
ACCORD. Action to control Cardiovascular Risks in Diabetes: Tight blood glucose control is also not the best treatment for diabetic cardiovascular disease:
The glycemia trial showed that tight blood glucose control was actually worse than keeping higher glucose levels. This caused the glycemia trial to be terminated early due to accelerated deaths. N Engl J Med 2008;358:2545-59.
Practicing Physicians Know: For some time, it was assumed that diabetic patients were “cheating” and thus cause their diabetic milieu. However, not every patient is non-controlled, some are obsessive about blood sugar, but still the complications arise, sooner or later. This is because improper metabolism causes improper inflammatory responses.
What Trina achieves by replicating and mimicking the non-diabetic pancreas is something that no compound has ever been able to accomplish, normal cellular energy (ATP) level, with their automatic reduction of lipid metabolism and the reversal of diabetic inflammatory processes. No other treatment has achieved the outcomes which follow because no other technology mimics the normal pancreas signals to the liver/body, and no other technology is even close to doing so.
All Published Studies since after 2000 have uniformly shown that normal pancreas secretion is in “bursts every 4 to 6 minutes, with an amplitude of 660% of baseline.
As shown above/right, the Trina treatment provides similar insulin waves from an IV access, and was doing so over 10 years before it was widely known that the pancreas delivered all insulin in oscillation bursts. This treatment is very different from subcutaneous insulin by either pump or shot.
Tested in University Settings: APT has been tested in a number of university centers of excellence including Harvard (Joselin), University of California Davis, University of Arizona, Scripps, Temple University, and the Mayo Clinic, just to name a few (see publications). APT is main-stream medicine, seeking only to provide the body with proper stimulation, and thus allowing the body to achieve its own repair. All of the clinical trials addressing outcomes used the generally accepted standards for assessing patient outcomes.
Treatment. Patients treat for 4-5 hours in the clinic once a week for at least 6 months. After the 6 month period, treatment is continued every 2 weeks thereafter. The 4 to 5 hours of treatment twice a month is cost effective and a small price to pay for uniquely better heath. Patients enjoy clinic due to their new quality of life, energy, mental abilities and the real expectation of stopping the complications of diabetes, the “Second Bite of the Apple.”
During a treatment day, 3 one hour infusions are given with the patient sitting in a recliner chair but still able to walk around etc. During the treatments, carbohydrates and intravenous insulin are administered using the Bionica programmed infusion device. The patient stays in the treatment area, and continues to read, watch TV, type, compute, telephone or engage in any other passive activities. Many patients enjoy coming into the clinic early in the morning, and being finished by shortly after lunch time.
Uniquely Dramatic Patient Outcomes: The Trina treatment does not produce subtle, marginal improvement. It is effective even for the severely ill. This is gratifying for diabetes practitioners who in the past have only been able to watch the disease progress.
Objective of APT Treatment: The treatment works by returning patients to a more normal resting metabolism, thereby addressing the core problem of diabetes, elevated lipid use and metabolic inflammation. Once cells have the ATP (energy) to achieve repair, the DNA of the cells know what to do, and do it because the metabolic inflammatory process is also arrested. No physician who has worked with APT during the clinical trials has reported any negative outcomes. They uniformly understand the logic of providing the natural stimulation needed to metabolize properly.
Treatment Outcomes: The treatment is independently clinically proven safe and effective for the major complications of diabetes including kidney disease, cardiovascular disease, wound healing, retinopathy, hypertension, neuropathy, and the general maladies of diabetes including lack of wellbeing, energy, sleep, sexual functions and the likes. With deficient metabolism it is not surprising that widespread basic biochemical abnormalities exist. The fundamental body-wide defect is the reduced ability of glucose to be used as a fuel for body tissues, and a corresponding increase in lipid use. Diabetic people fail to metabolize carbohydrates and thus lose 30% of the potential cellular energy. And, by metabolizing lipids, proteins and free fatty acids are correctly characterized as “butter burners”. Unlike conventional treatment where the patient is starved of appropriate carbohydrates, patients on the Artificial Pancreas Treatment® metabolize carbohydrates and can eat more normal and healthy foods as their bodies can burn carbohydrates.
When the core problem of resting carbohydrate metabolism is addressed, it is reasonable that widespread and diverse outcomes would occur, and they do. All of the long-term studies have shown a significant improvement and stopping, retarding and then reversing all major complications of diabetes. No study using the Trina treatment has been a failure. Because the therapy works at a body-wide cellular level restoring metabolic integrity and energy production in all cells, the logical assumption is that each cell’s DNA undertakes to repair itself and its organs, causing damage reversal.
One uniform benefit is the greatly improved sense of well-being and energy. Feeling normal and physically well is unique to ATP. Most people with diabetes have forgotten what it feels like to feel well as they have slowly deteriorated over time. With APT they often say that they just did not realize how sickly they had become until they felt normal again.
Safety: Both the treatment and the unique Bionica infusion pump have flawless safety records, with no adverse reactions, no claims, no recalls, malpractice suits or anything negative stemming from the treatment. Every person with diabetes complications will benefit from the APT treatment. APT is fully developed, rolled out in a “turn-key” manner, and is ready to treat millions of critically ill people.
Conclusion: The result of all the prior work is that with the opening of clinics the Artificial Pancreas Treatment® is becoming one of the most important medical advancements of this decade. All that is needed is to roll out clinics where medical professionals will help many needful people with the Artificial Pancreas Treatment®.
|Insulin, Glucagon and Glucose Exhibit Synchronous Sustained Oscillations in Fasting Monkeys; Science 1977 195: 177-179||As early as 1923, fluctuations of sugars were found. However, this is the first publication where oscillations of insulin were found. It was so unique, it made Science.|
|Cyclic oscillations of basal plasma glucose and insulin concentrations in human beings. Lang DA, Matthews DR, Peto, J, Turner RC NEJM 1979 301:1023-1027||This was the first human trial to measure at one minute intervals the insulin levels (top line) and found them to be “significantly greater than expected”|
|Brief, Irregular Oscillations of Basal Plasma Insulin and Glucose Concentrations in Diabetic Man Lang DA, Matthews DR, Burnet M, Turner RC Diabetes 1981; 30: 435- 439||This 1981 human study showed that normal insulin oscillations occurred in normal patients, and blunted in even mild maturity onset diabetes patients. The first clue that the loss of oscillations was part of diabetes.|
|Pulsatile Insulin Has Greater Hypoglycemic Effect than Continuous Delivery Matthews DR, Naylor BA, Jones RG Ward GM, Turner RC, Diabetes 1983 30:617-621||This study showed pulsed infused insulin had a greater glucose reducing effect than a steady infusion.|
|Efficacy of Pulsatile Versus Continuous Insulin Administration on Hepatic Glucose Production and Glucose Utilization in Type 1 Diabetic Humans. Bratusch-Marrain PR, Komjati M Waldhausl WK. Diabetes 1986 35:922-26||This study compared pulse infusion to continuous infusion. “In humans, various hormones e.g. insulin, glucagon, growth hormone, and luteinizing hormone are secreted in pulsatile fashion.” (It is now obvious) “The Cyclic mode of insulin secretion has a biologic advantage in regulating glucose metabolism.”|
|Pulsatility of insulin and glucagon release: physiological significance and pharmacological implications. Lefebvre PJ, Paolisso G, Scheen A, Henquin. Diabetologia 1987;30:443-53||The effects of insulin were significantly more marked when delivered in IV pulsatile manner than when continuous.|
|Effects of Prolonged Pulsatile Hyperinsulinemia in Humans, Enhancement of Insulin Sensitivity. Ward GM, Walters JM, Aitken PM, Best JD, Alford FP Diabetes 1990 39:501- 507||Prolonged IV pulsatile infusion has agreater hypoglycemic effects than continuous insulin infusion, a 55% greater effect.|
|Pulsatile insulin delivery has greater metabolic effects than continuous hormone administration in man: importance of pulse frequency. Paolisso G, Scheen A, Giugliano D, et al. JCEM 1991;72:607-615||Perhaps most telling of all, pulse (burst) insulin of the same amount inhibited hepatic endogenous glucose production as compared to 26 minute infusion delivery.|
|Glucose-induced amplitude regulation of pulsatile insulin secretion from individual pancreatic islets. Bergsten P and Hellman B. Diabetes 1993; M42: 670-4.||Insulin secretion by single islet cells of animals as glucose increased, resulted in pulses of insulin. Aptitudes increased, but frequency remained the same. This shows frequency of bursts is a signal irrespective of glucose levels.|
|Oscillary Insulin Secretion After Pancreas Transplant. O’Meara NM, Sturis J, et al Diabetes 1993 42:855-61||After transplant pulse aptitude was not different. Importantly this article confirms that “in many in vivo studies have demonstrated that insulin is released in a pulsatile fashion, and cites 7 papers.|
|Pulsatile (burst) insulin secretion accounts for 70% of total insulin secretion during fasting. Porksen N, Munn S, Steers J, et al. Am J Physiol. 1995; 269:E478-88||After transplant pulse aptitude was not different. Importantly this article confirms that “in many in vivo studies have demonstrated that insulin is released in a pulsatile fashion, and cites 7 papers.|
|Effects of Glucose Ingestion versus Infusion on Pulsatile Insulin Secretion. Porksen N, Munn SR, Steers JL, Veldhuis D, Butler PC. Diabetes 1996 45:1317-23||“Physiological studies further indicate that insulin is secreted in high frequency, discrete insulin secretory bursts.” Portal vein studies in humans are not practical”…but 8 years later Butler did just that. All studies show the importance of burst (pulses).|
|Mechanism of Sulfonylurea’s Stimulation of Insulin in Vivo. Selective Amplification of Insulin Secretory Burst Mass. Porksen N, Munn SR, Steers JL, Schmitz O, Veldhuis JD, Butler PC. Diabetes 1996 45:1792-97||Sulfonylurea class of drugs are commonly prescribed. “In summary we report that tolbutamide stimulated insulin secretion in vivo primarily by enhancing the pulsatile mode of insulin secretion.”|
|Glucagon-Like Peptide 1 Increases Mass but not Frequency or Orderliness of Pulsatile Insulin Secretion. Porksen N, Grofte T, Nyholm, et al. Diabetes 1998 47:45-49||“Insulin is secreted in a series of punctuated secretory bursts superimposed on a basal insulin release.” and later, “These bursts “resulting in high-frequency insulin concentration oscillations in the peripheral circulation.|
|Pathophysiology of Impaired Pulsatile Insulin Release. Bergsten, P, Diabetes Metab Res Rev 2000 16:179- 191||“Plasma insulin displays 5-10 min oscillations. In type 2 diabetes the regularity of the oscillations disappears, which may lead to insulin receptior down-regulation and glucose intolearance, and explain why pulsatile delivery has a greater hypoglycemic effect than continuous delivery.”|
|Glucagon-Like Peptide 1 Increases Secretory Burst Mass of Pulsatile Insulin Secretion in Patients with Type 2 Diabetes and Impaired Glucose Toerance. Ritzel R, Schulte M, Porksen N, Nauck M, Holst J, Juhl C, Marz W, Schmitz O, Schiegel WH, Nauck M. Diabetes 2001 50:776-784||“GLP-1 increases secretory burst mass and the amplitude of pulsatile insulin secretion in healthy volunteers without affecting burst frequency.” As of this point, every scientist has acknowledged the existence and importance of burst (pulse) insulin !|
|Acute and Short-Term Administration of Sulfonylurea Increases Pulsatile Insulin Secretion in Type 2 Diabetes. Juhl CB, Porkson N, Pincus SM, Hansen AP, Velhuis JD, Schmitz O. Diabetes 2001 50: 1778-84||“High frequency oscillatory patter of insulin release is disturbed in type 2 diabetes…Insulin pulsatility was assessed by 1-min interval. The agent augments insulin secretion by concurrently increasing pulse mass and basal insulin secretion without changing pulse mass and basal insulin secretion frequency or regularity.”|
|Do Oscillations of Insulin Secretion Occur in the Absence of Cytoplasmic Ca2+ Oscillations in β-Cells? Kjems LL, Ravier MA, Jonas JC, Henquin JC Diabetes 2002, 51 s177-182||“Insulin secretion is characterized by a pulsatility that is reflected by oscillation of plasma insulin concentrations”|
|Direct Measurement of Pulsatile Insulin Secretion from the Portal Vein in Human Subjects. Song, SH, McIntyre SS, Shah H, Veldhuis JD, Hayes PC, Butler, PC. JCEM 2002; 85:4491-99||“Insulin is secreted in high frequency pulses.” Quantification is complex, In the present study we measured pulsatile insulin release directly into the portal vein. Direct sampling caused the conclusion that insulin is humans has an interval of approximately 5 minutes.|
|Pulsatile Insulin secretion by human pancreatic islets. Song, SH, Kjems L, Ritzel R, et al. JCEM 2002; 87: 213-221||“Insulin is secreted in discrete bursts. These pulses are also present with islets are perfused.” Perfused single or groups of islet cells exhibited an interval of 6-8 min., comparable to that observed in humans in vivo.|
|Pulsatile Insulin Release From Islets Isolated From Three Subjects with Type 2 Diabetes. Lin J-M, Fabregat ME, Gomis R, Bergsten P. Diabetes 2002 51:988-993||“Plasma insulin in healthy subjects shows regular oscillations, which are important for the hypoglycemic action.” It is concluded that islets from the 3 individuals with T2DM release insulin in pulses.|
|Repaglinide Treatment Amplifies First-phase Insulin Secretion and High-frequency Pulsatile Insulin Release in Type 2 Diabetes. Hollingdal M, Sturis J, Gall MA, Damsbo P, Pincust S, et al. Diabetic Medicine 2005 22:1408-13||“First-phase insulin release and coordinated insulin pulsatility are disturbed in type 2 diabetes.” Repaglinide provides a modest first phase increase.|
|Pulsatility of Insulin Release- A Clinically Important Phenomenon. Helman, B et. al. Upsala Journal of Medical Sciences 2009 114:193-205||The islets the β-cells are mutually entrained into a common rhythm by gap junctions and diffusible factors. Synchronization of the different islet in the pancreas is supposed to be due to adjustment of the oscillations to the same phase by output of acetylcholine and ATP. (Thus the “Clinically Important Phenomenon”)|
|Pulsatile Portal Vein Insulin Delivery Enhances Hepatic Insulin Action and Signaling. Matveyenko AV, Liuwantara D, Gurlo T, Dirakossian D, Man CD, Cobelli C, et al. Diabetes 2012 61:2269-2279||“Insulin is secreted as discrete insulin secretory bursts at ~ 5 min intervals into the hepatic portal vein. These pulses being attenuated early in the development of type 1 and type 2 diabetes mellitus.” This is important for hepatic insulin action.|
|Loss of Pulsatile Insulin Secretion: A Factor in the Pathogenesis of type 2 Diabetes? Wahren J, Kallas A. Diabetes 2012 61:2228-2229||Insulin is secreted into the portal vein in a pulsatile fashion with approximately 5-min cycles (Fig. 1) Insulin pulses may account for as much as 70% of the total insulin secretion in the basal state. This pulsatile b-cell secretion pattern is controlled by an intrinsic rhythm of intracellular Ca2+ oscillations.|