Aoki Diabetes Research Institute

 

MAT^®    bibliography

This includes most published papers about clinical effects of metabolic activation therapy ( MAT^® treatment.)  Because metabolic activation therapy has had many names, published papers have referred to it as hepatic activation, chronic intermittent intravenous insulin therapy (CIIIT) or pulsatile intravenous insulin therapy (PIVIT).   This list includes studies from various institutions.

 Overviews

  1. Chronic intermittent intravenous insulin therapy: A new frontier in diabetes therapy. Aoki TT, Grecu EO, Arcangeli MA, Benbarka MM, Prescott P, Ahn JH. Diabetes Technology and Therapeutics 2001; 3(1): 111-123.

   2. Long-term intermittent intravenous  insulin therapy and type 1 diabetes mellitus.
Aoki TT, Benbarka MM, Okimura MC, Arcangeli MA,
Walter RM Jr, Wilson LD, Truong MP, Barber AR,
Kumagai LF. Lancet. 1993 Aug 28;342(8870):515-8.

  3. Type I diabetes: The ‘sleeping liver’ hypothesis and its clinical implications. Aoki TT, Benbarka MM. Modern Medicine 1992 60:73-76.

  4. Type I diabetes: An intensive approach
to controlling blood glucose levels. Aoki TT,
Benbarka MM. 1992 Modern Medicine 60:88-103.
 

Nephropathy

 1. Effects of pulsatile intravenous insulin therapy on the progression of diabetic nephropathy. Dailey GE, Boden GH, Creech RH, Johnson DG, Gleason RE, Kennedy FP, Weinrauch LA, Weir M, D'Elia JA. Metabolism 2000; 49: 1491-1495.

A multi-center randomized controlled trial in patients with Type 1 diabetes and diabetic nephropathy compared outcomes in 23 patients treated with pulsatile intravenous insulin therapy (MAT^® treatment) plus intensive insulin therapy compared to 26 patients treated with intensive insulin therapy alone. Blood pressure was controlled in both groups and patients were seen weekly. Hemoglobin A1c levels declined significantly in both groups. However, the rate of decline of the Creatinine Clearance level was significantly less (2.2 mL/min/yr) in the treatment group(MAT^® treatment  plus intensive insulin therapy) as compared to 7.7 mL/min/yr in the control group( intensive insulin therapy alone.) Projected average-time-until-dialysis/transplant is 5.2 years for the control group and 18.2 years for the MAT® treatment  group. Conclusion: MAT^® treatment appears to markedly reduce the progression of diabetic nephropathy.

  2. Effect of intensive insulin therapy on progression of overt nephropathy in patients with Type I diabetes mellitus. Aoki TT, Grecu EO, Gollapudi GM, Barber RA, Arcangeli MA, Benbarka MM, Prescott P, Meisenheimer R. Endocrine Practice 1999; 5: 174-8.

In patients with advanced diabetic kidney disease, the gradual deterioration of kidney function (decrease of creatinine clearance [CrCl] by 8-10 ml/min/year) cannot be arrested with "routine" insulin therapy. This study reports the treatment outcome of an average of 37 months (range 1-7 years) of MAT® treatment  in 31 patients with Type I diabetes and advanced diabetic renal disease. The CrCl at the end of the treatment period was essentially unchanged, suggesting that adding weekly MAT® treatment  to daily intensive insulin therapy could arrest or markedly delay progression to the end stage renal disease, when kidney dialysis or transplantation is required.

   3. A pilot study to test the effect of pulsatile insulin infusion on cardiovascular mechanisms that might contribute to attenuation
of renal compromise in type 1 diabetes mellitus patients with proteinuria. Weinrauch LA, Burger AJ, Aepfelbacher F, Lee AT, Gleason RE, D''Elia JA. Metabolism. 2007 Nov; 56(11):1453-7.

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Hypoglycemia

1. Long-term intermittent intravenous insulin therapy and type I diabetes mellitus. Aoki TT, Benbarka MM, Okimura MC, Arcangeli MA, Walter RM Jr., Wilson LD, Truong MP, Barber AR, Kumagai.  Lancet 1993; 342: 515-8.

A study of 20 diabetic patients over 42 months showed that MAT^® treatment resulted in a 98 percent decrease in major hypoglycemic reactions. On treatment with MAT^® treatment , patients with "brittle" diabetes and "hypoglycemia unawareness" gradually regained the ability to detect falling blood glucose levels. These patients went from an average of 3 severe hypoglycemic reactions (requiring outside intervention) per month to an average of 0.1 episodes per month. The average frequency of hypoglycemic reactions returned to three per month when MAT^® treatment  was stopped.

Hypertension

  1.Effect of chronic intermittent intravenous insulin therapy on anti-hypertensive medication requirements in IDDM subjects with hypertension and nephropathy. Aoki TT, Grecu EO, Prendergast JJ, Arcangeli MA, Meisenheimer R.  Diabetes Care 1995; 18: 1260-5.

MAT^® treatment for patients with high blood pressure led to a 46% decrease in the amount of medication required to control the patients' blood pressure.

  2. Effect of intensive insulin therapy on abnormal circadian blood pressure pattern in patients with Type 1 diabetes mellitus. Aoki, TT, Grecu EO, Arcangeli MA, Meisenheimer R. The Online Journal of Current Clinical Trials, 1995; Dec. 13: Doc. No.199.

Patients with severe diabetes often have increased night time blood pressure, a condition that may worsen the complications of diabetes. Patients in randomized, controlled clinical trials comparing two treatments 1) four subcutaneous insulin injections daily, vs 2) weekly MAT^® treatments added to the four subcutaneous injections daily had monthly measures of 24 hour ambulatory blood pressure. The group on weekly MAT^® treatment in addition to four subcutaneous insulin injections daily had a 3% decline in the night/day blood pressure ratio. In contrast, those on only four subcutaneous injections daily had a 3% increase in night/day blood pressure ratio. In addition, the group on MAT^® treatment had an significant improvement in the average HbA1c levels.

 

Hypotension

1. Chronic intermittent intravenous insulin therapy corrects orthostatic hypotension of diabetes. Aoki TT, Grecu EO, Arcangeli MA. Amer.  J. Med. 1995; 99: 683-4.

On MAT^® treatment, patients reported complete relief from dizziness and fainting when they stood up and blood pressure no longer dropped precipitously with upright posture.

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Obstetrics

1. The effect of chronic intermittent intravenous insulin therapy on pregnancy outcome in insulin dependent diabetes mellitus. Field N, Boe N, Gilbert W, Benbarka M, Aoki T.  Journal Soc. Gynecol. Invest. 1997; 4(1, supplement): 196A.

A group of 3 insulin-dependent diabetic pregnant patients received MAT^® treatment in addition to the usual regimen of 3 insulin shots per day and home glucose monitoring. Compared to 15 matched controls, the MAT^® treatment group all had normal hemoglobin A1c levels at delivery, none developed hypertensive complications requiring early delivery, and none required extra antepartum hospital days. Infants of the MAT^® treatment group were not hypoglycemic, and 2 of the 3 were discharged at the same time as their mothers.

Quality of Life

 

Physiology and Biochemistry

1. Acute insulin effects on plasma homocysteine levels in patients with diabetes mellitus. Aoki TT, Grecu EO, Medina M, Goodman M.  J Invest Med (in Press).

2. IGF-1 and IGFBP-1 blood levels in type 1 diabetes mellitus on intensive intravenous insulin therapy.  Aoki TT, Grecu EO.  J Invest Med, 1999; 47(2) 78 A.(abstract).

3. Restoration of glucose homeostasis in insulin-dependent diabetic subjects. An inducible process. Foss MC, Vlachokosta FV, Cunningham LN, Aoki TT.  Diabetes 1982; 31: 46-52.

4. Role of muscle in CO2 production after oral glucose administration in man. Meistas MT, Vlachokosta FV, Gleason RE, Arcangeli M, Aoki TT.  Diabetes 1985; 34: 960-63.

5. Evidence for restoration of hepatic glucose processing in type I diabetes mellitus. Aoki TT, Vlachokosta FV, Foss MC, Meistas MI.Journal of Clinical Investigation 1983; 71:837-839.